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                       Radioisotopes in Medicine


The Understanding the Atom Series

Nuclear energy is playing a vital role in the life of every man, woman,
and child in the United States today. In the years ahead it will affect
increasingly all the peoples of the earth. It is essential that all
Americans gain an understanding of this vital force if they are to
discharge thoughtfully their responsibilities as citizens and if they
are to realize fully the myriad benefits that nuclear energy offers
them.

The United States Atomic Energy Commission provides this booklet to help
you achieve such understanding.

                  [Illustration: Edward J. Brunenkant]

                                          Edward J. Brunenkant, Director
                                       Division of Technical Information


UNITED STATES ATOMIC ENERGY COMMISSION

  Dr. Glenn T. Seaborg, Chairman
  James T. Ramey
  Wilfrid E. Johnson
  Dr. Theos J. Thompson
  Dr. Clarence E. Larson




                       Radioisotopes in Medicine


by Earl W. Phelan




                                CONTENTS


  INTRODUCTION                                                          1
      History                                                           1
      What Is Radiation?                                                5
      What Is Radioactivity?                                            5
      What Are Radioisotopes?                                           6
      How Are Radioisotopes Used?                                       7
      What Do We Mean by Tracer Atoms?                                  9
  DIAGNOSIS                                                            11
      Pinpointing Disease                                              11
      Arsenic-74                                                       14
      Chromium-51                                                      15
      Cobalt-60                                                        16
      Iodine-131                                                       18
      Iron-59                                                          23
      Phosphorus-32                                                    24
      Sodium-24                                                        25
      Technetium-99^{_m_}                                              26
      Thulium-170 and Gamma Radiography                                27
      Tritium                                                          28
      Activation Analysis                                              30
      Summary                                                          30
  THERAPY                                                              31
      A Successful Case                                                31
      General Principles                                               32
      Iodine-131 and Iodine-132                                        32
      Boron-10                                                         33
      Phosphorus-32                                                    35
      Gold-198                                                         37
      Beads, Needles, and Applicators                                  38
      Teletherapy                                                      41
  CONCLUSIONS                                                          43
  APPENDIX                                                             44
  SUGGESTED REFERENCES                                                 47

                 United States Atomic Energy Commission
                   Division of Technical Information
           Library of Congress Catalog Card Number: 66-62749
                                  1966

[Illustration: THE COVER

This multi-detector positron scanner is used to locate tumors. A
radioisotope-labeled substance is injected into the body and
subsequently concentrates in the tumor tissue. The radioisotope emits
positrons that immediately decay and produce two gamma rays that travel
in opposite directions. These rays are detected simultaneously on a pair
of opposing detection crystals and a line is established along which the
tumor is located. This method is one of many ways doctors use
radioisotopes to combat disease. In this, as in many other procedures
described in this booklet, the patient remains comfortable at all
times.]

[Illustration: THE AUTHOR

Earl W. Phelan is Professor of Chemistry at Tusculum College,
Greeneville, Tennessee. From 1952 to 1965, he served as Staff Assistant
in the Laboratory Director’s Office at Argonne National Laboratory,
where his duties included editing the Argonne Reviews and supplying
information to students. For 22 years prior to moving to Argonne he
served as Head of the Chemistry Department of the Valdosta State College
In Georgia. He received his B.S. and Ph.D. degrees from Cornell
University.]




                                               Radioisotopes in Medicine


                                                       By EARL W. PHELAN




                              INTRODUCTION


History

The history of the use of radioisotopes for medical purposes is filled
with names of Nobel Prize winners. It is inspiring to read how great
minds attacked puzzling phenomena, worked out the theoretical and
practical implications of what they observed, and were rewarded by the
highest honor in science.

For example, in 1895 a German physicist, Wilhelm Konrad Roentgen,
noticed that certain crystals became luminescent when they were in the
vicinity of a highly evacuated electric-discharge tube. Objects placed
between the tube and the crystals screened out some of the invisible
radiation that caused this effect, and he observed that the greater the
density of the object so placed, the greater the screening effect. He
called this new radiation X rays, because _x_ was the standard algebraic
symbol for an unknown quantity. His discovery won him the first Nobel
Prize in physics in 1901.

[Illustration: _Wilhelm Roentgen_]

A French physicist, Antoine Henri Becquerel, newly appointed to the
chair of physics at the Ecole Polytechnique in Paris, saw that this
discovery opened up a new field for research and set to work on some of
its ramifications. One of the evident features of the production of X
rays was the fact that while they were being created, the glass of the
vacuum tube gave off a greenish phosphorescent glow. This suggested to
several physicists that substances which become phosphorescent upon
exposure to visible light might give off X rays along with the
phosphorescence.

Becquerel experimented with this by exposing various crystals to
sunlight and then placing each of them on a black paper envelope
enclosing an unexposed photographic plate. If any X rays were thus
produced, he reasoned, they would penetrate the wrapping and create a
developable spot of exposure on the plate. To his delight, he indeed
observed just this effect when he used a phosphorescent material,
uranium potassium sulfate. Then he made a confusing discovery. For
several days there was no sunshine, so he could not expose the
phosphorescent material. For no particular reason (other than that there
was nothing else to do) Becquerel developed a plate that had been in
contact with uranium material in a dark drawer, even though there had
been no phosphorescence. The telltale black spot marking the position of
the mineral nevertheless appeared on the developed plate! His conclusion
was that uranium in its normal state gave off X rays or something
similar.

[Illustration: _Henri Becquerel_]

At this point, Pierre Curie, a friend of Becquerel and also a professor
of physics in Paris, suggested to one of his graduate students, his
young bride, Marie, that she study this new phenomenon. She found that
both uranium and thorium possessed this property of radioactivity, but
also, surprisingly, that some uranium minerals were more radioactive
than uranium itself. Through a tedious series of chemical separations,
she obtained from pitchblende (a uranium ore) small amounts of two new
elements, polonium and radium, and showed that they possessed far
greater radioactivity than uranium itself. For this work Becquerel and
the two Curies were jointly awarded the Nobel Prize in physics in 1903.

[Illustration: _Pierre and Marie Curie_]

At the outset, Roentgen had noticed that although X rays passed through
human tissue without causing any immediate sensation, they definitely
affected the skin and underlying cells. Soon after exposure, it was
evident that X rays could cause redness of the skin, blistering, and
even ulceration, either in single doses or in repeated smaller doses. In
spite of the hazards[1] involved, early experimenters determined that X
rays could destroy cancer tissues more rapidly than they affected
healthy organs, so a basis was established quite soon for one of
Medicine’s few methods of curing or at least restraining cancer.

The work of the Curies in turn stimulated many studies of the effect of
radioactivity. It was not long before experimenters learned that
naturally radioactive elements—like radium—were also useful in cancer
therapy. These elements emitted gamma rays,[2] which are like X rays but
usually are even more penetrating, and their application often could be
controlled better than X rays. Slowly, over the years, reliable methods
were developed for treatment with these radioactive sources, and
instruments were designed for measuring the quantity of radiation
received by the patient.

[Illustration: _Frederic and Irene Joliot-Curie_]

The next momentous advance was made by Frederic Joliot, a French chemist
who married Irene Curie, daughter of Pierre and Marie Curie. He
discovered in 1934 that when aluminum was bombarded with alpha
particles[3] from a radioactive source, emission of positrons (positive
electrons) was induced. Moreover, the emission continued long after the
alpha source was removed. This was the first example of artificially
induced radioactivity, and it stimulated a new flood of discoveries.
Frederic and Irene Joliot-Curie won the Nobel Prize in chemistry in 1935
for this work.

Others who followed this discovery with the development of additional
ways to create artificial radioactivity were two Americans, H. Richard
Crane and C. C. Lauritsen, the British scientists, John Cockcroft and E.
T. S. Walton, and an American, Robert J. Van de Graaff. Ernest O.
Lawrence, an American physicist, invented the cyclotron (or “atom
smasher”), a powerful source of high-energy particles that induced
radioactivity in whatever target materials they impinged upon. Enrico
Fermi, an Italian physicist, seized upon the idea of using the newly
discovered neutron (an electrically neutral particle) and showed that
bombardment with neutrons also could induce radioactivity in a target
substance. Cockcroft and Walton, Lawrence, and Fermi all won Nobel
Prizes for their work.

Patient application of these new sources of bombarding particles
resulted in the creation of small quantities of hundreds of radioactive
isotopic species, each with distinctive characteristics. In turn, as we
shall see, many ways to use radioisotopes have been developed in medical
therapy, diagnosis, and research. By now, more than 3000 hospitals hold
licenses from the Atomic Energy Commission to use radioisotopes. In
addition, many thousands of doctors, dentists, and hospitals have X-ray
machines that they use for some of the same broad purposes. One of the
results of all this is that every month new uses of radioisotopes are
developed.

More persons are trained every year in methods of radioisotope use and
more manufacturers are producing and packaging radioactive materials.
This booklet tells some of the successes achieved with these materials
for medical purposes.


What Is Radiation?

Radiation is the propagation of radiant energy in the form of waves or
particles. It includes electromagnetic radiation ranging from radio
waves, infrared heat waves, visible light, ultraviolet light, and X rays
to gamma rays. It may also include beams of particles of which
electrons, positrons, neutrons, protons, deuterons, and alpha particles
are the best known.[4]


What Is Radioactivity?

It took several years following the basic discovery by Becquerel, and
the work of many investigators, to systematize the information about
this phenomenon. Radioactivity is defined as the property, possessed by
some materials, of spontaneously emitting alpha or beta particles or
gamma rays as the unstable (or radioactive) nuclei of their atoms
disintegrate.


What Are Radioisotopes?

[Illustration: _Frederick Soddy_]

In the 19th Century an Englishman, John Dalton, put forth his atomic
theory, which stated that all atoms of the same element were exactly
alike. This remained unchallenged for 100 years, until experiments by
the British chemist, Frederick Soddy, proved conclusively that the
element neon consisted of two different kinds of atoms. All were alike
in chemical behavior but some had an atomic weight (their mass relative
to other atoms) of 20 and some a weight of 22. He coined the word
_isotope_ to describe one of two or more atoms having the same atomic
number but different atomic weights.[5]

Radioisotopes are isotopes that are unstable, or radioactive, and give
off radiation spontaneously. Many radioisotopes are produced by
bombarding suitable targets with neutrons now readily available inside
atomic reactors. Some of them, however, are more satisfactorily created
by the action of protons, deuterons, or other subatomic particles that
have been given high velocities in a cyclotron or similar accelerator.

Radioactivity is a process that is practically uninfluenced by any of
the factors, such as temperature and pressure, that are used to control
the rate of chemical reactions. The rate of radioactive decay appears to
be affected only by the structure of the unstable (decaying) nucleus.
Each radioisotope has its own half-life, which is the time it takes for
one half the number of atoms present to decay. These half-lives vary
from fractions of a second to millions of years, depending only upon the
atom. We shall see that the half-life is one factor considered in
choosing a particular isotope for certain uses.

[Illustration: HALF-LIFE PATTERN OF STRONTIUM-90]

 Percent of        100         50          25         12.5        6.75
 Radioactivity
                Beginning       1           2           3           4
                 of Life   Half-life   Half-lives  Half-lives  Half-lives
                            28 years    56 years    84 years    112 years

Most artificially made radioisotopes have relatively short half-lives.
This makes them useful in two ways. First, it means that very little
material is needed to obtain a significant number of disintegrations. It
should be evident that, with any given number of radioactive atoms, the
number of disintegrations per second will be inversely proportional to
the half-life. Second, by the time 10 half-lives have elapsed, the
number of disintegrations per second will have dwindled to ¹/₁₀₂₄ the
original number, and the amount of radioactive material is so small it
is usually no longer significant. (Note the decrease in the figure
above.)


How Are Radioisotopes Used?

A radioisotope may be used either as a source of radiation energy
(energy is _always_ released during decay), or as a tracer: an
identifying and readily detectable marker material. The location of this
material during a given treatment can be determined with a suitable
instrument even though an unweighably small amount of it is present in a
mixture with other materials. On the following pages we will discuss
medical uses of individual radioisotopes—first those used as tracers and
then those used for their energy. In general, tracers are used for
analysis and diagnosis, and radiant-energy emitters are used for
treatment (therapy).

Radioisotopes offer two advantages. First, they can be used in extremely
small amounts. As little as one-billionth of a gram can be measured with
suitable apparatus. Secondly, they can be directed to various definitely
known parts of the body. For example, radioactive sodium iodide behaves
in the body just the same as normal sodium iodide found in the iodized
salt used in many homes. The iodine concentrates in the thyroid gland
where it is converted to the hormone thyroxin. Other radioactive, or
“tagged”, atoms can be routed to bone marrow, red blood cells, the
liver, the kidneys, or made to remain in the blood stream, where they
are measured using suitable instruments.[6]

Of the three types of radiation, alpha particles (helium nuclei) are of
such low penetrating power that they cannot be used for measurement from
outside the body. Beta particles (electrons) have a moderate penetrating
power, therefore they produce useful therapeutic results in the vicinity
of their release, and they can be detected by sensitive counting
devices. Gamma rays are highly energetic, and they can be readily
detected by counters—radiation measurement devices—used outside the
body.

[Illustration: _Relative penetration of alpha, beta, and gamma
radiation._]

For comparison, a sheet of paper stops alpha particles, a block of wood
stops beta particles, and a thick concrete wall stops gamma rays.

In one way or another, the key to the usefulness of radioisotopes lies
in the energy of the radiation. When radiation is used for treatment,
the energy absorbed by the body is used either to destroy tissue,
particularly cancer, or to suppress some function of the body. Properly
calculated and applied doses of radiation can be used to produce the
desired effect with minimum side reactions. Expressed in terms of the
usual work or heat units, ergs or calories, the amount of energy
associated with a radiation dose is small. The significance lies in the
fact that this energy is released in such a way as to produce important
changes in the molecular composition of individual cells within the
body.


What Do We Mean by Tracer Atoms?

When a radioisotope is used as a tracer, the energy of the radiation
triggers the counting device, and the exact amount of energy from each
disintegrating atom is measured. This differentiates the substance being
traced from other materials naturally present.

[Illustration: _This is the first photoscanner, which was developed in
1954 at the University of Pennsylvania and was retired from service in
1963. When gamma rays emitted by a tracer isotope in the patient’s body
struck the scanner, a flashing light produced a dot on photographic
film. The intensity of the light varied with the counting rate and thus
diseased tissues that differed little from normal tissue except in their
uptake of an isotope could be discerned._]

With one conspicuous exception, it is impossible for a chemist to
distinguish any one atom of an element from another. Once ordinary salt
gets into the blood stream, for example, it normally has no
characteristic by which anyone can decide what its source was, or which
sodium atoms were added to the blood and which were already present. The
exception to this is the case in which some of the atoms are “tagged” by
being made radioactive. Then the radioactive atoms are readily
identified and their quantity can be measured with a counting device.

A radioactive tracer, it is apparent, corresponds in chemical nature and
behavior to the thing it traces. It is a true part of it, and the body
treats the tagged and untagged material in the same way. A molecule of
hemoglobin carrying a radioactive iron atom is still hemoglobin, and the
body processes affect it just as they do an untagged hemoglobin
molecule. The difference is that a scientist can use counting devices to
follow the tracer molecules wherever they go.

[Illustration: _One of the first scans made by a photoscanner. The
photorecording (dark bands), superimposed on an X-ray picture for
orientation, shows radioactivity in a cancer in the patient’s neck._]

It should be evident that tracers used in _diagnosis_—to identify
disease or improper body function—are present in such small quantities
that they are relatively harmless. Their effects are analogous to those
from the radiation that every one of us continually receives from
natural sources within and without the body. _Therapeutic_ doses—those
given for medical treatment—by contrast, are given to patients with a
disease that is in need of control, that is, the physician desires to
destroy selectively cells or tissues that are abnormal. In these cases,
therefore, the skill and experience of the attending physician must be
applied to limit the effects to the desired benefits, without damage to
healthy organs.

This booklet is devoted to these two functions of radioisotopes,
_diagnosis_ and _therapy_; the field of medical research using
radioactive tools is so large that it requires separate coverage.[7]




                               DIAGNOSIS


Pinpointing Disease

Mr. Peters, 35-year-old father of four and a resident of Chicago’s
northwest side, went to a Chicago hospital one winter day after
persistent headaches had made his life miserable. Routine examinations
showed nothing amiss and his doctor ordered a “brain scan” in the
hospital’s department of nuclear medicine.

Thirty minutes before “scan time”, Mr. Peters was given, by intravenous
injection, a minute amount of radioactive technetium. This radiochemical
had been structured so that, if there were a tumor in his cranium, the
radioisotopes would be attracted to it. Then he was positioned so an
instrument called a scanner could pass close to his head.

As the motor-driven scanner passed back and forth, it picked up the
gamma rays being emitted by the radioactive technetium, much as a Geiger
counter detects other radiation. These rays were recorded as black
blocks on sensitized film inside the scanner. The result was a piece of
exposed film that, when developed, bore an architectural likeness or
image of Mr. Peters’ cranium.

[Illustration: _The inset picture shows a brain scan made with a
positron scintillation camera. A tumor is indicated by light area above
ear. (Light area in facial region is caused by uptake in bone and
extracellular space.) The photograph shows a patient, completely
comfortable, receiving a brain scan on one of the three rectilinear
scanning devices in the nuclear medicine laboratory of a hospital._]

Mr. Peters, who admitted to no pain or other adverse reaction from the
scanning, was photographed by the scanner from the front and both sides.
The procedure took less than an hour. The developed film showed that the
technetium had concentrated in one spot, indicating definitely that a
tumor was present. Comparison of front and side views made it possible
to pinpoint the location exactly.

Surgery followed to remove the tumor. Today, thanks to sound and early
diagnosis, Mr. Peters is well and back on the job. His case is an
example of how radioisotopes are used in hospitals and medical centers
for diagnosis.

[Illustration: _The first whole body scanner, which was developed at the
Donner Laboratory in 1952 and is still being used. The lead collimator
contains 10 scintillation counters and moves across the subject. The bed
is moved and serial scans are made and then joined together to form a
head-to-toe picture of the subject._]

[Illustration: _The diagram shows a scan and the parts of a scanner.
(Also see page 21.)_]

In one representative hospital, 17 different kinds of radioisotope
measurements are available to aid physicians in making their diagnoses.
All the methods use tracer quantities of materials. Other hospitals may
use only a few of them, some may use even more. In any case they are
merely tools to augment the doctors’ skill. Examples of measurements
that can be made include blood volume, blood circulation rate, red blood
cell turnover, glandular activity, location of cancerous tissue, and
rates of formation of bone tissue or blood cells.

Of the more than 100 different radioisotopes that have been used by
doctors during the past 30 years, five have received by far the greatest
attention. These are iodine-131, phosphorus-32, gold-198, chromium-51,
and iron-59. Some others have important uses, too, but have been less
widely employed than these five. The use of individual radioisotopes in
making important diagnostic tests makes a fascinating story. Typical
instances will be described in the following pages.

[Illustration: _A differential multi-detector developed at Brookhaven
National Laboratory locates brain tumors with positron-emitting
isotopes. By using many pairs of detection crystals, the device shortens
the scanning time and increases accuracy. (See cover for another type of
positron scanner.)_]


Arsenic-74

Brain tumors tend to concentrate certain ions (charged atoms or
molecules). When these ions are gamma-ray emitters, it is possible to
take advantage of the penetrating power of their gamma rays to locate
the tumor with a scanning device located outside the skull.

Arsenic-74 and copper-64 are isotopes emitting _positrons_,[8] which
have one peculiar property. Immediately after a positron is emitted from
a nucleus it decays, producing two gamma rays that travel in exactly
opposite directions. The scanning device has two detectors called
scintillation counters, one mounted on each side of the patient’s head.

The electrical circuitry in the scanner is such that only those gamma
rays are counted that impinge simultaneously on both counters. This
procedure eliminates most of the “noise”, or scattered and background
radiation.


Chromium-51

Because chromium, in the molecule sodium chromate, attaches itself to
red blood cells, it is useful in several kinds of tests. The procedures
are slightly complicated, but yield useful information. In one, a sample
of the patient’s blood is withdrawn, stabilized with heparin (to prevent
clotting) and incubated with a tracer of radioactive sodium chromate.
Excess chromate that is not taken up by the cells is reduced and washed
away. Then the radioactivity of the cells is measured, just before
injection into the patient. After a suitable time to permit thorough
mixing of the added material throughout the blood stream, a new blood
sample is taken and its radioactivity is measured. The total volume of
red blood cells then can be calculated by dividing the total
radioactivity of the injected sample by the activity per milliliter of
the second sample.

[Illustration: _Spleen scans made with red blood cells, which had been
altered by heat treatment and tagged with chromium-51. Such damaged
cells are selectively removed by the spleen. A is a normal spleen. B
shows an abscess in the spleen. Note dark ring of radioactivity
surrounding the lighter area of decreased activity at the central
portion of spleen._]

In certain types of anemia the patient’s red blood cells die before
completing the usual red-cell lifetime of about 120 days. To diagnose
this, red cells are tagged with chromium-51 (⁵¹Cr) in the manner just
described. Then some of them are injected back into the patient and an
identical sample is injected into a compatible normal individual. If the
tracer shows that the cells’ survival time is too short in both
recipients to the same degree, the conclusion is that the red cells
themselves must be abnormal. On the other hand, if the cell-survival
time is normal in the normal individual and too short in the patient,
the diagnosis is that the patient’s blood contains some substance that
destroys the red cells.

When chromium trichloride, CrCl₃, is used as the tagging agent, the
chromium is bound almost exclusively to plasma proteins, rather than the
red cells. Chromium-51 may thus be used for estimating the volume of
plasma circulating in the heart and blood vessels. The same type of
computation is carried on for red cells (after correction for a small
amount of chromium taken up by the red blood cells). This procedure is
easy to carry out because the radioactive chromium chloride is injected
directly into a vein.

An ingenious automatic device has been devised for computing a patient’s
total blood volume using the ⁵¹Cr measurement of the red blood cell
volume as its basis. This determination of total blood volume is of
course necessary in deciding whether blood or plasma transfusions are
needed in cases involving bleeding, burns, or surgical shock. This ⁵¹Cr
procedure was used during the Korean War to determine how much blood had
been lost by wounded patients, and helped to save many, many lives.

For several years, iodine-131 has been used as a tracer in determining
cardiac output, which is the rate of blood flow from the heart. It has
appeared recently that red blood cells tagged with ⁵¹Cr are more
satisfactory for this measurement than iodine-labeled albumin in the
blood serum. It is obvious that the blood-flow rate is an extremely
important physiological quantity, and a doctor must know it to treat
either heart ailments or circulatory disturbances.

In contrast to the iodine-131 procedure, which requires that an artery
be punctured and blood samples be removed regularly for measurement,
chromium labeling merely requires that a radiation counter be mounted on
the outside of the chest over the aorta (main artery leaving the heart).
A sample of labeled red blood cells is introduced into a vein, and the
recording device counts the radioactivity appearing in the aorta as a
function of time. Eventually, of course, the counting rate (the number
of radioactive disintegrations per second) levels off when the indicator
sample has become mixed uniformly in the blood stream. From the shape of
the curve on which the data are recorded during the measurements taken
before that time, the operator calculates the heart output per second.

[Illustration: _In this cardiac output study a probe is positioned over
the heart and the passage of iodine-131 labeled human serum albumin
through this area is recorded._]

Obstetricians caring for expectant mothers use red cells tagged with
⁵¹Cr to find the exact location of the placenta. For example, in the
condition known as _placenta previa_, the placenta—the organ within the
uterus by which nourishment is transferred from the mother’s blood to
that of the unborn child—may be placed in such a position that fatal
bleeding can occur. A radiation-counting instrument placed over the
lower abdomen gives information about the exact location of the
placenta. If an abnormal situation exists, the attending physician is
then alert and ready to cope with it. The advantages of chromium over
iodine-131, which has also been used, are that smaller doses are
required, and that there is no transfer of radioactivity to the fetal
circulation.

Still another common measurement using ⁵¹Cr-labeled red blood cells is
the determination of the amount and location of bleeding from the
gastrointestinal tract (the stomach and bowels). The amount is found by
simple measurement of chromium in the blood that appears in the stools.
To find the location is slightly more complicated. The intestinal
contents are sampled at different levels through an inserted tube, and
the radiation of the samples determined separately.

Finally, gastrointestinal loss of protein can be measured with the aid
of ⁵¹Cr-labeled blood serum. The serum is treated with CrCl₃ and then
injected into a vein. In several very serious ailments there is serious
loss of blood protein through the intestines. In these conditions the
⁵¹Cr level in the intestinal excretions is high, and this alerts the
doctor to apply remedial measures.


Cobalt-60

Vitamin B₁₂ is a cobalt compound. Normally the few milligrams of B₁₂ in
the body are stored in the liver and released to the blood stream as
needed. In _pernicious anemia_, a potentially fatal but curable disease,
the B₁₂ content of the blood falls from the usual level of 300-900
micromicrograms per milliliter (ml) to 0 to 100 micromicrograms per ml.
The administration of massive doses of B₁₂ is the only known remedy for
this condition.

If the B₁₂ is labeled with radioactive cobalt, its passage into the
blood stream may be observed by several different methods. The simplest
is to give the B₁₂ by mouth, and after about 8 hours study the level of
cobalt radioactivity in the blood. Cobalt-60 has been used for several
years, but recently cobalt-58 has been found more satisfactory. It has a
half-life of 72 days while ⁶⁰Co has a 5.3-year half-life. This reduces
greatly the amount of radiation to the patient’s liver by the retained
radioactivity.


Iodine-131

Like chromium-51, iodine is a versatile tracer element. It is used to
determine blood volume, cardiac output, plasma volume, liver activity,
fat metabolism, thyroid cancer metastases, brain tumors, and the size,
shape, and activity of the thyroid gland.

[Illustration: _A linear photoscanner produced these pictures of (A) a
normal thyroid, (B) an enlarged thyroid, and (C) a cancerous thyroid._]

Because of its unique connection with the thyroid gland, iodine-131 is
most valuable in measurements connected with that organ. Thyroxin, an
iodine compound, is manufactured in the thyroid gland, and transferred
by the blood stream to the body tissues. The thyroxin helps to govern
the oxygen consumption of the body and therefore helps control its
metabolism. Proper production of thyroxin is essential to the proper
utilization of nutrients. Lowered metabolism means increased body
weight. Lowered thyroid activity may mean expansion of the gland,
causing one form of goiter.

Iodine-131 behaves in the body just as the natural non-radioactive
isotope, iodine-127, does, but the radioactivity permits observation
from outside the body with some form of radiation counter. Iodine can
exist in the body in many different chemical compounds, and the counter
can tell where it is but not in what form. Hence chemical manipulation
is necessary in applying this technique to different diagnostic
procedures.

The thyroid gland, which is located at the base of the neck, is very
efficient in trapping inorganic iodide from the blood stream,
concentrating and storing the iodine-containing material and gradually
releasing it to the blood stream in the form of protein-bound iodine
(PBI).

One of the common diagnostic procedures for determining thyroid
function, therefore, is to measure the percentage of an administered
dose of ¹³¹I that is taken up by the gland. Usually the patient is given
a very small dose of radioactive sodium iodide solution to drink, and
two hours later the amount of iodine in the gland is determined by
measuring the radiation coming from the neck area. In hyperthyroidism,
or high thyroid gland activity, the gland removes iodide ions from the
blood stream more rapidly than normal.

[Illustration: Screening test for Hyperthyroidism

Oral dose ¹³¹I

Graph of Uptake in 1 hour (Percent of administered dose) versus Uptake
in 24 hours (Percent of administered dose)]

[Illustration: _It is especially important in isotope studies on infants
and small children that the radiation exposure be low. By carrying out
studies in the whole body counter room, the administered dose can be
greatly reduced. The photographs illustrate a technique of measuring
radioiodine uptake in the thyroid gland with extremely small amounts of
a mixture of iodine-131 and iodine-125. A shows a small television set
that is mounted above the crystal in such a way that good viewing
requires that the head be kept in the desired position. This helps solve
the problem of keeping small children still during a 15-minute counting
period. B shows a child in position for a thyroid uptake study._]

This simple procedure has been used widely. One difficulty in using it
is that its success is dependent upon the time interval between
injection and measurement. An overactive gland both concentrates iodine
rapidly and also discharges it back to the blood stream as PBI more
rapidly than normal. Modifications of the test have been made to compare
the amount of iodine-131 that was administered with the amount
circulating in the blood as PBI. The system acquires chemical separation
of the two forms of iodine from a sample of blood removed from a vein,
followed by separate counting. This computation of the “conversion
ratio” of radioactive plasma PBI to plasma-total ¹³¹I gives results that
are less subject to misinterpretation.

To determine local activity in small portions of the thyroid, an
automatic scanner is used. A collimator[9] shields the detector (a
Geiger-Müller tube or scintillating crystal) so that only those impulses
originating within a very small area are accepted by the instrument. The
detector is then moved back and forth slowly over the entire area and
the radiation is automatically recorded at definite intervals, creating
a “map” of the active area. In cases where lumps, or nodules, have been
discovered in the thyroid, the map is quite helpful in distinguishing
between cancerous and benign nodules. The former are almost always less
radioactive than surrounding tissues.

[Illustration: _Seven serial scans made with the whole body scanner were
put together to provide a whole body scan of this patient with thyroid
cancer that had spread to the lung. One millicurie of iodine-131 was
administered and the scan made 72 hours later. Note the uptake in the
lung. This patient was successfully treated with large doses of
iodine-131._]

Fragments of cancerous thyroid tissue may migrate to other parts of the
body and grow there. These new cancers are known as metastatic cancers
and are a signal of an advanced state of disease. In such a situation
even complete surgical removal of the original cancer may not save the
patient. If these metastases are capable of concentrating iodine (less
than 10% of them are), they can be located by scanning the whole body in
the manner that was just described. When a thyroid cancer is discovered,
therefore, a doctor may look for metastases before deciding to operate.

Human blood serum albumin labeled with ¹³¹I is used for measurement of
the volume of circulating plasma. The procedure is quite similar to that
used with radioactive chromium. Iodinated human serum albumin labeled
with ¹³¹I is injected into a vein. Then, after allowing time for
complete mixing of the sample with the blood, a second sample is counted
using a scintillation counter.

[Illustration: _Time-lapse motion pictures of the liver of a 3-year-old
girl were made with the scintillation camera 1 hour after injection of
50 microcuries of iodine-131-labeled rose bengal dye. This child was
born without a bile-duct system and an artificial bile duct had been
created surgically. She developed symptoms that caused concern that the
duct had closed. These scans show the mass of material containing the
radioactive material (small light area) moving downward and to the
right, indicating that the duct was still open._]

For many years, a dye known as _rose bengal_ has been used in testing
liver function. About 10 years ago this procedure was improved by
labeling the dye with ¹³¹I. When this dye is injected into a vein it
goes to the liver, which removes it from the blood stream and transfers
it to the intestines to be excreted. The rate of disappearance of the
dye from the blood stream is therefore a measure of the liver activity.
Immediately after administration of the radioactive dye, counts are
recorded, preferably continuously from several sites with shielded,
collimated detectors. One counter is placed over the side of the head or
the thigh to record the clearance of the dye from the blood stream. A
second is placed over the liver, and a third over the abdomen to record
the passage of the dye into the small intestine.

Human serum albumin labeled with ¹³¹I is sometimes used for location of
brain tumors. It appears that tumors alter a normal “barrier” between
the brain and blood in such a manner that the labeled albumin can
penetrate tumorous tissues although it would be excluded from healthy
brain tissue.

                        [Illustration: Showing:]

  1 Human serum albumin labeled with ¹³¹I
  2 Tumor selectively localizes labeled albumin
  3 Survey of gamma radiation (Standard points)

The brain behaves almost uniquely among body tissues in that a
“blood-brain barrier” exists, so that substances injected into the blood
stream will not pass into brain cells although they will pass readily
into muscular tissue. This blood-brain barrier does not exist in brain
tumors. A systematic scanning of the skull then permits location of
these cancerous “hot spots”.


Iron-59

Iron is a necessary constituent of red blood cells, so its radioactive
form, ⁵⁹Fe, has been used frequently in measurement of the rate of
formation of red cells, the lifetime of red cells, and red cell volumes.
The labeling is more difficult than labeling with chromium for the same
purposes, so this procedure no longer has the importance it once had.

On the other hand, direct measurement of absorption of iron by the
digestive tract can be accomplished only by using ⁵⁹Fe. In
_achlorhydria_ the gastric juice in the stomach is deficient in
hydrochloric acid, and this condition has been shown to lower the iron
absorption. A normal diet contains much more iron than the body needs,
but in special cases, sometimes called “tired blood” in advertising for
medicines, iron compounds are prescribed for the patient. If ⁵⁹Fe is
included, its appearance in the blood stream can be monitored and the
effectiveness of the medication noted.

[Illustration: _This multiple-port scintillation counter is used for
iron-kinetic studies. The tracer dose of iron-59 is administered into
the arm vein and then the activities in the bone marrow, liver, and
spleen are recorded simultaneously with counters positioned over these
areas, and show distribution of iron-59 as a function of time. When the
data are analyzed in conjunction with iron-59 content in blood,
information can be obtained about sites of red blood cell production and
destruction._]


Phosphorus-32

The phosphate ion is a normal constituent of the blood. In many kinds of
tumors, phosphates seem to be present in the cancerous tissue in a
concentration several times that of the surrounding healthy tissue. This
offers a way of using phosphorus-32 to distinguish between cancer cells
and their neighbors. Due to the fact that ³²P gives off beta rays but no
gammas, the counter must be placed very close to the suspected tissue,
since beta particles have very little penetrating power. This fact
limits the use of the test to skin cancers or to cancers exposed by
surgery.

Some kinds of brain tumors, for instance, are difficult to distinguish
visually from the healthy brain tissue. In such cases, the patient may
be given ³²P labeled phosphate intravenously some hours before surgery.
A tiny beta-sensitive probe counter then can be moved about within the
operative site to indicate to the surgeon the limits of the cancerous
area.


Sodium-24

Normal blood is about 1% sodium chloride or ordinary salt. This fact
makes possible the use of ²⁴Na in some measurements of the blood and
other fluids. The figure illustrates this technique. A sample of ²⁴NaCl
solution is injected into a vein in an arm or leg. The time the
radioisotope arrives at another part of the body is detected with a
shielded radiation counter. The elapsed time is a good indication of the
presence or absence of constrictions or obstructions in the circulatory
system.

                        [Illustration: Showing]

  1 ²⁴NaCl solution injected
  2 Blood carries ²⁴NaCl to both legs
  3 High reading—good circulation
  Site of constriction
  4 Low reading—poor circulation

The passage of blood through the heart may also be measured with the aid
of sodium-24. Since this isotope emits gamma rays, measurement is done
using counters on the outside of the body, placed at appropriate
locations above the different sections of the heart.

                        [Illustration: Showing:]

  1 ²⁴Na intravenously injected
  To lungs, To body, From arm, From right lung, From left lung
  2 Geiger counter detects radiations from ²⁴Na
  3 Ink writing recorder shows route of ²⁴Na


Technetium-99^{m}

Because of its short half-life of six hours, technetium-99^{m}[10] is
coming into use for diagnosis using scanning devices, particularly for
brain tumors. It lasts such a short time it obviously cannot be kept in
stock, so it is prepared by the beta decay of molybdenum-99.[11] A stock
of molybdenum is kept in a shielded container in which it undergoes
radioactive decay yielding technetium. Every morning, as the technetium
is needed, it is extracted from its parent by a brine solution. This
general procedure of extracting a short-lived isotope from its parent is
also used in other cases. We shall see later that radon gas is obtained
by an analogous method from its parent, radium.

[Illustration: _Using a “nuclear cow” to get technetium from its parent
isotope. The “cow” is being fed saltwater through a tube. The saltwater
drains through a high-radiation (hot) isotope. The resultant drip-off is
a daughter such as technetium-99^{m}. This new, mild isotope can be
mixed with other elements and these become the day’s supply of
radioisotopes for other scans. Technetium-99^{m} decays in 6 hours. Thus
greater amounts, with less possibility of injury, can be administered
and a better picture results._]


Thulium-170 and Gamma Radiography

For years it has been recognized that there would be many uses for a
truly portable device for taking X-ray pictures—one that could be
carried by the doctor to the bedside or to the scene of an accident.
Conventional X-ray equipment has been in use by doctors for many years,
and highly efficient apparatus has become indispensable, especially in
treating bone conditions. There is, however, a need for a means of
examining patients who cannot be moved to a hospital X-ray room, and are
located where electric current sources are not available.

A few years ago, a unit was devised that weighed only a few pounds, and
could take “X-ray pictures” (actually gamma radiographs) using the gamma
rays from the radioisotope thulium-170. The thulium source is kept
inside a lead shield, but a photographic shutter-release cable can be
pressed to move it momentarily over an open port in the shielding. The
picture is taken with an exposure of a few seconds. A somewhat similar
device uses strontium-90 as the source of beta radiation that in turn
stimulates the emission of gamma rays from a target within the
instrument.

[Illustration: _A technician holds an inexpensive portable X-ray unit
that was developed by the Argonne National Laboratory. Compare its size
with the standard X-ray machine shown at left and above._]

Still more recently, ¹²⁵I has been used very successfully in a portable
device as a low-energy gamma source for radiography. The gamma rays from
this source are sufficiently penetrating for photographing the arms and
legs, and the necessary shielding is easily supplied to protect the
operator. By contrast with larger devices, the gamma-ray source can be
as small as one-tenth millimeter in diameter, virtually a point source;
this makes possible maximum sharpness of image. The latest device, using
up to one curie[12] of ¹²⁵I, weighs 2 pounds, yet has adequate shielding
for the operator. It is truly portable.

If this X-ray source is combined with a rapid developing photographic
film, a physician can be completely freed from dependence upon the
hospital laboratory for emergency X rays. A finished print can be ready
for inspection in 10 seconds. The doctor thus can decide quickly whether
it is safe to move an accident victim, for instance. In military
operations, similarly, it becomes a simple matter to examine wounded
soldiers in the field where conventional equipment is not available.


Tritium

More than 30 years ago, when deuterium (heavy hydrogen) was first
discovered, heavy water (D₂O) was used for the determination of total
body water. A small sample of heavy water was given either intravenously
or orally, and time was allowed for it to mix uniformly with all the
water in the body (about 4 to 6 hours). A sample was then obtained of
the mixed water and analyzed for its heavy water content. This procedure
was useful but it was hard to make an accurate analysis of low
concentrations of heavy water.

More recently, however, tritium (³H) (radioactive hydrogen) has been
produced in abundance. Its oxide, tritiated water (³H₂O), is chemically
almost the same as ordinary water, but physically it may be
distinguished by the beta rays given off by the tritium. This very soft
(low-energy) beta ray requires the use of special counting equipment,
either a windowless flow-gas counter or a liquid scintillator, but with
the proper techniques accurate measurement is possible. The total body
water can then be computed by the general isotope dilution formula used
for measuring blood plasma volume.

[Illustration: _The total body water is determined by the dilution
method using tritiated water. This technician is purifying a urine
sample so that the tritium content can be determined and the total body
water calculated._]


Activation Analysis

Another booklet in this series, _Neutron Activation Analysis_, discusses
a new process by which microscopic quantities of many different
materials may be analyzed accurately. Neutron irradiation of these
samples changes some of their atoms to radioactive isotopes. A
multichannel analyzer instrument gives a record of the concentration of
any of about 50 of the known elements.

One use of this technique involved the analysis of a hair from
Napoleon’s head. More than 100 years after his death it was shown that
the French Emperor had been given arsenic in large quantities and that
this possibly caused his death.

The ways in which activation analysis can be applied to medical
diagnosis are at present largely limited to toxicology, the study of
poisons, but the future may bring new possibilities.

Knowledge is still being sought, for example, about the physiological
role played by minute quantities of some of the elements found in the
body. The ability to determine accurately a few parts per million of
“trace elements” in the various tissues and body fluids is expected to
provide much useful information as to the functions of these materials.


Summary

A large number of different radioisotopes have been used for measurement
of disease conditions in the human body. They may measure liquid
volumes, rates of flow or rates of transfer through organs or membranes;
they may show the behavior of internal organs; they may differentiate
between normal and malignant tissues. Hundreds of hospitals are now
making thousands of these tests annually.

This does not mean that all the diagnostic problems have been solved.
Much of the work is on an experimental rather than a routine basis.
Improvements in techniques are still being made. As quantities of
radioisotopes available for these purposes grow, and as the cost
continues to drop, it is expected there will be still more applications.
Finally, this does not mean we no longer need the doctor’s diagnostic
skill. All radioisotope procedures are merely tools to aid the skilled
physician. As the practice of medicine has changed from an art to a
science, radioisotopes have played a useful part.




                                THERAPY


A Successful Case

A doctor recently told this story about a cancer patient who was cured
by irradiation with cobalt-60.

“A 75-year-old white male patient, who had been hoarse for one month,
was treated unsuccessfully with the usual medications given for a bad
cold. Finally, examination of his larynx revealed an ulcerated swelling
on the right vocal cord. A biopsy (microscopic examination of a tissue
sample) was made, and it was found the swelling was a squamous-cell
cancer.

“Daily radiation treatment using a cobalt-60 device was started and
continued for 31 days. This was in September 1959. The cobalt-60 unit is
one that can be operated by remote control. It positions radioactive
cobalt over a collimator, which determines the size of the radiation
beam reaching the patient. The machine may be made to rotate around the
patient or can be used at any desired angle or position.

                        [Illustration: Showing:]

  ⁶⁰Co source
  Tungsten alloy shielding
  Shutter
  Counterweight and personnel shield

“When the treatment series was in progress, the patient’s voice was
temporarily made worse, but it returned to normal within two months
after the treatment ended. The radiation destroyed the cancerous growth,
and frequent examinations over 6 years since have failed to reveal any
regrowth.

“The treatment spared the patient’s vocal cords, and his voice, airway,
and food passage were preserved.”

This dramatic tale with a happy ending is a good one with which to start
a discussion of how doctors use radioisotopes for treatment of disease.


General Principles

Radioisotopes have an important role in the treatment of disease,
particularly cancer. It is still believed that cancer is not one but
several diseases with possible multiple causes. Great progress is being
made in development of chemicals for relief of cancer. Nevertheless,
radiation and surgery are still the main methods for treating cancer,
and there are many conditions in which relief can be obtained through
use of radiation. Moreover, the imaginative use of radioisotopes gives
much greater flexibility in radiation therapy. This is expected to be
true for some years to come even as progress continues.

Radioisotopes serve as concentrated sources of radiation and frequently
are localized within the diseased cells or organs. The dose can be
computed to yield the maximum therapeutic effect without harming
adjacent healthy tissues. Let us see some of the ways in which this is
done.


Iodine-131 and Iodine-132

Iodine, as was mentioned earlier, concentrates in the thyroid gland, and
is converted there to protein-bound iodine that is slowly released to
the blood stream. Iodine-131, in concentrations much higher than those
used in diagnostic tests, will irradiate thyroid cells, thereby damage
them, and reduce the activity of an overactive thyroid
(hyperthyroidism). The energy is released within the affected gland, and
much of it is absorbed there. Iodine-131 has a half-life of 8.1 days. In
contrast, ¹³²I has a half-life of only 2.33 hours. What this means is
that the same weight of radioactive ¹³²I will give a greater radiation
dose than ¹³¹I would, and lose its activity rapidly enough to present
much less hazard by the time the iodine is released to the blood stream.
Iodine-132 is therefore often preferred for treatment of this sort.


Boron-10

Boron-10 has been used experimentally in the treatment of inoperable
brain tumors. _Glioblastoma multiforme_, a particularly malignant form
of cancer, is an invariably fatal disease in which the patient has a
probable life expectancy of only 1 year. The tumor extends roots into
normal tissues to such an extent that it is virtually impossible for the
surgeon to remove all malignant tissue even if he removes enough normal
brain to affect the functioning of the patient seriously. With or
without operation the patient dies within months. This is therefore a
case in which any improvement at all is significantly helpful.

The blood-brain barrier that was mentioned earlier minimizes the
passages of many materials into normal brain tissues. But when some
organic or inorganic compounds, such as the boron compounds, are
injected into the blood stream, they will pass readily into brain tumors
and _not_ move into normal brain cells.

Boron-10 absorbs slow neutrons readily, and becomes boron-11, which
disintegrates almost immediately into alpha particles and a lithium
isotope. Alpha particles, remember, have very little penetrating power,
so all the energy of the alpha radioactivity is expended within the
individual tumor cells. This is an ideal situation, for it makes
possible destruction of tumor cells with virtually no harm to normal
cells, even when the two kinds are closely intermingled.

Slow neutrons pass through the human body with very little damage, so a
fairly strong dose of them can be safely applied to the head. Many of
them will be absorbed by the boron-10, and maximum destruction of the
cancer will occur, along with minimum hazard to the patient. This
treatment is accomplished by placing the head of the patient in a beam
of slow neutrons emerging from a nuclear reactor a few minutes after the
boron-10 compound has been injected into a vein.

[Illustration: SEQUENCE OF EVENTS IN NEUTRON CAPTURE THERAPY USING
BORON-10

_Neutron capture treatment of a brain tumor, using the Brookhaven
National Laboratory research reactor (center)._]

  Control console
  Treatment port (shutter shown open)
  Observation window
  Patient treatment room
  Shutter elevator (hydraulic)
  Control rod drives
  Heavy concrete shield
  Control rods
  Experimental holes
  Reactor core
  Cooling air
  Cooling water

[Illustration: _(1) A lead shutter shields the patient from reactor
neutrons._]

[Illustration: _(2) A compound containing the stable element boron is
injected into the bloodstream; the tumor absorbs most of the boron._]

[Illustration: _(3) After 8 minutes, when the tumor is saturated, the
shutter is removed and neutrons bombard the brain, splitting boron atoms
so that fragments destroy tumor tissue._]

[Illustration: _(4) Twenty minutes later the shutter is closed and the
treatment ends._]

The difficulty is that most boron compounds themselves are poisonous to
human tissues, and only small concentrations can be tolerated in the
blood. Efforts have been made, with some success, to synthesize new
boron compounds that have the greatest possible degree of selective
absorption by the tumors. Both organic and inorganic compounds have been
tried, and the degree of selectivity has been shown to be much greater
for some than for others. So far it is too early to say that any cures
have been brought about, but results have been very encouraging. The
ideal drug, one which will make possible complete destruction of the
cancer without harming the patient, is probably still to be devised.


Phosphorus-32

Another disease which is peculiarly open to attack by radioisotopes is
_polycythemia vera_. This is an insidious ailment of a chronic, slowly
progressive nature, characterized by an abnormal increase in the number
of red blood cells, an increase in total blood volume, enlargement of
the spleen, and a tendency for bleeding to occur. There is some
indication that it may be related to leukemia.

Until recent years there was no very satisfactory treatment of this
malady. The ancient practice of bleeding was as useful as anything,
giving temporary relief but not striking at the underlying cause. There
is still no true cure, but the use of phosphorus-32 has been very
effective in causing disappearance of symptoms for periods from months
to years, lengthening the patient’s life considerably. The purpose of
the ³²P treatment (using a sodium-radiophosphate solution) is not to
destroy the excess of red cells, as had been tried with some drugs, but
rather to slow down their formation and thereby get at the basic cause.

Phosphorus-32 emits pure beta rays having an average path in tissue only
2 millimeters long. Its half-life is 14.3 days. When it is given
intravenously it mixes rapidly with the circulating blood and slowly
accumulates in tissues that utilize phosphates in their metabolism. This
brings appreciable concentration in the blood-forming tissues (about
twice as much in blood cells as in general body cells).

                        [Illustration: Showing:]

  1 Patient drinks ³²P in water solution
  2 ³²P selectively absorbed
  Blood cell production in bone marrow

[Illustration: _Survival of_ polycythemia vera _patients after ³²P
therapy_.]

  No. cases                       201
  Average age                      52
  Median survival                13.2
  Survival for
     5 years                    91.5%
     10 years                   70.0%

One other pertinent fact is that these rapidly dividing hematopoietic
cells are extremely sensitive to radiation. (Hematopoietic cells are
those that are actively forming blood cells and are therefore those that
should be attacked selectively.) The dose required is of course many
times that needed for diagnostic studies, and careful observation of the
results is necessary to determine that exactly the desired effect has
been obtained.

There exists some controversy over this course of treatment. No one
denies that the lives of patients have been lengthened notably.
Nevertheless since the purpose of the procedure is to reduce red cell
formation, there exists the hazard of too great a reduction, and the
possibility of causing leukemia (a disease of too few red cells). There
may be a small increase in the number of cases of leukemia among those
treated with ³²P compared with the general population. The controversy
arises over whether the ³²P treatment _caused_ the leukemia, or whether
it merely prolonged the lives of the patients until leukemia appeared as
it would have in these persons even without treatment. This is probably
quibbling, and many doctors believe that the slight unproven risk is
worth taking to produce the admitted lengthy freedom from symptoms.


Gold-198

The last ailment we shall discuss in this section is the accumulation of
large quantities of excess fluid in the chest and abdominal cavities
from their linings, as a consequence of the growth of certain types of
malignant tumors.

Frequent surgical drainage was at one time the only very useful
treatment, and of course this was both uncomfortable and dangerous. The
use of radioactive colloidal suspensions, primarily colloidal gold-198,
has been quite successful in palliative treatment: It does not cure, but
it does give marked relief.

                        [Illustration: Showing:]

  Colloidal gold in shield
  Saline solution
  To peritoneal or pleural cavity

Radioactive colloids (a colloid is a suspension of one very finely
divided substance in some other medium) can be introduced into the
abdominal cavity, where they may remain suspended or settle out upon the
lining. In either case, since they are not dissolved, they do not pass
through the membranes or cell walls but remain within the cavity.
Through its destructive and retarding effect on the cancer cells the
radiation inhibits the oozing of fluids.

Gold-198 offers several advantages in such cases. It has a short
half-life (2.7 days); it is chemically inert and therefore nontoxic; and
it emits beta and gamma radiation that is almost entirely absorbed by
the tissues in its immediate neighborhood.

The results have been very encouraging. There is admittedly no evidence
of any cures, or even lengthening of life, but there has been marked
reduction of discomfort and control of the oozing in over two-thirds of
the cases treated.


Beads, Needles, and Applicators

Radium salts were the first materials to be used for radiation treatment
of cancer. Being both very expensive and very long-lived, they could not
be injected but were used in temporary implants. Radium salts in powder
form were packed into tiny hollow needles about 1 centimeter long, which
were then sealed tightly to prevent the escape of radon gas. As radium
decays (half-life 1620 years) it becomes gaseous radon. The latter is
also radioactive, so it must be prevented from escaping. These gold
needles could be inserted into tumors and left there until the desired
dosage had been administered. One difficulty in radium treatment was
that the needles were so tiny that on numerous occasions they were lost,
having been thrown out with the dressings. Then, both because of their
value and their hazard, a frantic search ensued when this happened, not
always ending successfully.

[Illustration: _The needle used for implantation of yttrium-90 pellets
into the pituitary gland is shown in the top photograph. In the center X
ray the needle is in place and the pellets have just been passed through
it into the bone area surrounding the pituitary gland. The bottom X ray
shows the needle withdrawn and the pellets within the bone._]

The fact that radon, the daughter of radium, is constantly produced from
its parent, helped to eliminate some of this difficulty. Radium could be
kept in solution, decaying constantly to yield radon. The latter, with a
half-life of 4 days, could be sealed into gold seeds 3 by 0.5
millimeters and left in the patient without much risk, even if he failed
to return for its removal at exactly the appointed time. The cost was
low even if the seeds were lost.

During the last 20 years, other highly radioactive sources have been
developed that have been used successfully. Cobalt-60 is one popular
material. Cobalt-59 can be neutron-irradiated in a reactor to yield
cobalt-60 with such a high specific activity that a small cylinder of it
is more radioactive than the entire world’s supply of radium. Cobalt-60
has been encapsulated in gold or silver needles, sometimes of special
shapes for adaptation to specific tumors such as carcinoma of the
cervix. Sometimes needles have been spaced at intervals on plastic
ribbon that adapts itself readily to the shape of the organ treated.

Gold-198 is also an interesting isotope. Since it is chemically inert in
the body, it needs no protective coating, and as is the case with radon,
its short half-life makes its use simpler in that the time of removal is
not of critical importance.

Ceramic beads made of yttrium-90 oxide are a moderately new development.
One very successful application of this material has been for the
destruction of the pituitary gland.

Cancer may be described as the runaway growth of cells. The secretions
of the pituitary gland serve to stimulate cell reproduction, so it was
reasoned that destruction of this gland might well slow down growth of a
tumor elsewhere in the body. The trouble was that the pituitary is small
and located at the base of the brain. Surgical removal had brought
dramatic relief (not cure) to many patients, but the surgery itself was
difficult and hazardous. Tiny yttrium-90 oxide beads, glasslike in
nature, can be implanted directly in the gland with much less difficulty
and risk, and do the work of destroying the gland with little damage to
its surroundings. The key to the success of yttrium-90 is the fact that
it is a beta-emitter, and beta rays have so little penetrating power
that their effect is limited to the immediate area of the implant.


Teletherapy

Over 200 teletherapy units are now in use in the United States for
treatment of patients by using very high intensity sources of cobalt-60
(usually) or cesium-137. Units carrying sources with intensities of more
than a thousand curies are common.

[Illustration: _The cobalt-60 unit at the M. D. Anderson Hospital and
Tumor Institute in Houston, Texas, employs a 3000-curie source. This
unit has a mechanism that allows for rotation therapy about a stationary
patient. Many different treatment positions are possible. This patient,
shown in position for therapy, has above her chest an auxiliary
diaphragm that consists of an expanded metal tray on which blocks of
either tungsten or lead are placed to absorb gamma rays and thus shape
the field of treatment. In this case they allow for irradiation of the
portions of the neck and chest delineated by the lines visible on the
patient._]

Since a curie is the amount of radioactivity in a gram of radium that is
in equilibrium with its decay products, a 1000-curie source is
comparable to 2 pounds of pure radium. Neglecting for the moment the
scarcity and enormous cost of that much radium (millions of dollars), we
have to consider that it would be large in volume and consequently
difficult to apply. Radiation from such a quantity cannot be focussed;
consequently, either much of it will fall upon healthy tissue
surrounding the cancer or much of it will be wasted if a narrow passage
through the shield is aimed at the tumor. In contrast, a tiny cobalt
source provides just as much radiation and more if it can be brought to
bear upon the exact spot to be treated.

              [Illustration: Diagram of teletherapy unit]

Most interesting of all is the principle by which internal cancers can
be treated with a minimum of damage to the skin. Deep x-irradiation has
always been the approved treatment for deep-lying cancers, but until
recently this required very cumbersome units. With the modern rotational
device shown in the diagram, a very narrow beam is aimed at the patient
while the source is mounted upon a carrier that revolves completely
around him. The patient is positioned carefully so that the lesion to be
treated is exactly at the center of the circular path of the carrier.
The result is that the beam strikes its internal target during the
entire circular orbit, but the same amount of radiation is spread out
over a belt of skin and tissue all the way around the patient. The
damage to any one skin cell is minimized. The advantage of this device
over an earlier device, in which the patient was revolved in a
stationary beam, is that the mechanical equipment is much simpler.




                              CONCLUSIONS


In summary, then, we may say that radioisotopes play an important role
in medicine. For the diagnostician, small harmless quantities of many
isotopes serve as tools to aid him in gaining information about normal
and abnormal life processes. The usefulness of this information depends
upon his ingenuity in devising questions to be answered, apparatus to
measure the results, and explanations for the results.

For therapeutic uses, on the other hand, the important thing to remember
is that radiation damages many kinds of cells, especially while they are
in the process of division (reproduction).[13] Cancer cells are
self-reproducing cells, but do so in an uncontrolled manner. Hence
cancer cells are particularly vulnerable to radiation. This treatment
requires potent sources and correspondingly increases the hazards of
use.

In all cases, the use of these potentially hazardous materials belongs
under the supervision of the U. S. Atomic Energy Commission.[14]
Licenses are issued by the Commission after investigation of the
training, ability, and facilities possessed by prospective users of
dangerous quantities. At regular intervals courses are given to train
individuals in the techniques necessary for safe handling, and graduates
of these courses are now located in laboratories all over the country.

The future of this field cannot be predicted with certainty. Research in
hundreds of laboratories is continuing to add to our knowledge, through
new apparatus, new techniques, and new experiments. Necessarily the
number of totally new fields is becoming smaller, but most certainly the
number of cases using procedures already established is bound to
increase. We foresee steady improvement and growth in all uses of
radioisotopes in medicine.




                                APPENDIX


Measuring Instruments[15]

The measurement of radioactivity must be accomplished indirectly, so use
is made of the physical, chemical, and electrical effects of radiation
on materials. One commonly used effect is that of ionization. Alpha and
beta particles ionize gases through which they pass, thereby making the
gases electrically conductive. A family of counters uses this principle:
the ionization chamber, the proportional counter, and the Geiger-Müller
counter.

Certain crystals, sodium iodide being an excellent example, emit flashes
of visible light when struck by ionizing radiation. These crystals are
used in scintillation counters.


Ionization Chambers

One of a pair of electrodes is a wire located centrally within a
cylinder. The other electrode is the wall of the chamber. Radiation
ionizes the gas within the chamber, permitting the passage of current
between the electrodes. The thickness of a window in the chamber wall
determines the type of radiation it can measure. Only gamma rays will
pass through a heavy metal wall, glass windows will admit all gammas and
most betas, and plastic (Mylar) windows are necessary to admit alpha
particles. Counters of this type, when properly calibrated, will measure
the total amount of radiation received by the body of the wearer.


Proportional Counters

This is a type of ionization chamber in which the intensity of the
electrical pulse it produces is proportional to the energy of the
incoming particle. This makes it possible to record alpha particles and
discriminate against gamma rays.


Geiger-Müller Counters

These have been widely used and are versatile in their applications. The
potential difference between the electrodes in the Geiger-Müller tube
(similar to an ionization chamber) is high. A single alpha or beta
particle ionizes some of the gas within the chamber. In turn these ions
strike other gas molecules producing secondary ionization. The result is
an “avalanche” or high-intensity pulse of electricity passing between
the electrodes. These pulses can be counted electrically and recorded on
a meter at rates up to several thousand per minute.


Scintillation Counters

Since the development of the photoelectric tube and the photomultiplier
tube (a combination of photoelectric cell and amplifier), the
scintillation counter has become the most popular instrument for most
purposes described in this booklet. The flash of light produced when an
individual ionizing particle or ray strikes a sodium-iodide crystal is
noted by a photoelectric cell. The intensity of the flash is a measure
of the energy of the radiation, so the voltage of the output of the
photomultiplier tube is a measure of the wavelength of the original
gamma ray. The scintillation counter can observe up to a million counts
per minute and discriminate sharply between gamma rays of different
energies. With proper windows it can be used for alpha or beta counts as
well.


Solid State Counters

The latest development is a tiny silicon (transistor-type) diode
detector that can be made as small as a grain of sand and placed within
the body with very little discomfort.


Scanners

Many of the applications described in this booklet require accurate
knowledge of the exact location of the radioactive source within the
body. Commonly a detecting tube is used having a collimating shield so
that it accepts only that radiation that strikes it head-on. A
motor-driven carrier moves the counter linearly at a slow rate.
Radiation is counted and whenever the count reaches the predetermined
amount—from one count to many—an electric impulse causes a synchronously
moving pen to make a dot on a chart. The scanner, upon reaching the end
of a line moves down to the next line and starts over, eventually
producing a complete record of the radiation sources it has passed over.




                          SUGGESTED REFERENCES


Technical Books

  _Radioactive Isotopes in Medicine and Biology_, Solomon Silver, Lea &
  Febiger, Philadelphia, Pennsylvania 19106, 1962, 347 pp., $8.00.

  _Atomic Medicine_, Charles F. Behrens and E. Richard King (Eds.), The
  Williams & Wilkins Company, Baltimore, Maryland 21202, 1964, 766 pp.,
  $18.00.

  _The Practice of Nuclear Medicine_, William H. Blahd, Franz K. Bauer,
  and Benedict Cassen, Charles C. Thomas, Publisher, Springfield,
  Illinois 62703, 1958, 432 pp., $12.50.

  _Progress in Atomic Medicine_, John H. Lawrence (Ed.), Grune &
  Stratton, Inc., New York 10016, 1965, volume 1, 240 pp., $9.75.

  _Radiation Biology and Medicine_, Walter D. Claus (Ed.),
  Addison-Wesley Publishing Company, Reading, Massachusetts 01867, 1958,
  944 pp., $17.50. Part 7, Medical Uses of Atomic Radiation, pp.
  471-589.

  _Radioisotopes and Radiation_, John H. Lawrence, Bernard Manowitz, and
  Benjamin S. Loeb, McGraw-Hill Book Company, New York 10036, 1964, 131
  pp., $18.00. Chapter 1, Medical Diagnosis and Research, pp. 5-45;
  Chapter 2, Medical Therapy, pp. 49-62.


Popular Books

  _Atoms Today and Tomorrow_ (revised edition), Margaret O. Hyde,
  McGraw-Hill Book Company, Inc., New York 10036, 1966, 160 pp., $3.25.
  Chapter 9, The Doctor and the Atom, pp. 79-101.

  _Atomic Energy in Medicine_, K. E. Halnan, Philosophical Library,
  Inc., New York 10016, 1958, 157 pp., $6.00. (Out of print but
  available through libraries.)

  _Teach Yourself Atomic Physics_, James M. Valentine, The Macmillan
  Company, New York 10011, 1961, 192 pp., $1.95. (Out of print but
  available through libraries.) Chapter X, Medical and Biological Uses
  of Radioactive Isotopes, pp. 173-184.

  _Atoms for Peace_, David O. Woodbury, Dodd, Mead & Company, New York
  10016, 1965, 259 pp., $4.50. Pp. 174-191.

  _The Atom at Work_, Jacob Sacks, The Ronald Press Company, New York
  10010, 1956, 341 pp., $5.50. Chapter 13, Radioactive Isotopes in
  Hospital and Clinic, pp. 244-264.


Articles

  Ionizing Radiation and Medicine, S. Warren, _Scientific American_,
  201: 164 (September 1959).

  Nuclear Nurses Learn to Tame the Atom, W. McGaffin, _Today’s Health_,
  37: 62 (December 1959).

  How Isotopes Aid Medicine in Tracking Down Your Ailments, J. Foster,
  _Today’s Health_, 42: 40 (May 1964).

  Nuclear Energy as a Medical Tool, G. W. Tressel, _Today’s Health_, 43:
  50 (May 1965).


Reports

  _Radioisotopes in Medicine_ (SRIA-13), Stanford Research Institute,
  Clearinghouse for Federal Scientific and Technical Information, 5285
  Port Royal Road, Springfield, Virginia 22151, 1959, 180 pp., $3.00.

The following reports are available from the Superintendent of
Documents, U. S. Government Printing Office, Washington, D. C. 20402.

  _Isotopes and Radiation Technology_ (Fall 1963), P. S. Baker, A. F.
  Rupp, and Associates, Oak Ridge National Laboratory, U. S. Atomic
  Energy Commission, 123 pp., $0.70.

  _Radioisotopes in Medicine_ (ORO-125), Gould A. Andrews, Marshall
  Brucer, and Elizabeth B. Anderson, 1956, 817 pp., $6.00.

  _Applications of Radioisotopes and Radiation in the Life Sciences_,
  Hearings before the Subcommittee on Research, Development, and
  Radiation of the Joint Committee on Atomic Energy, 87th Congress, 1st
  Session, 1961, 513 pp., $1.50; Summary Analysis of the Hearings, 23
  pp., $0.15.


Motion Pictures

Available for loan without charge from the AEC Headquarters Film
Library, Division of Public Information, U. S. Atomic Energy Commission,
Washington, D. C. 20545 and from other AEC film libraries.

  _Radioisotope Applications in Medicine_, 26 minutes, black and white,
  sound, 1964. Produced by the Educational Broadcasting Corporation
  under the joint direction of the U. S. Atomic Energy Commission’s
  Divisions of Isotopes Development and Nuclear Education and Training,
  and the Oak Ridge Institute of Nuclear Studies. This film traces the
  development of the use of radioisotopes and radiation in the field of
  medicine from the early work of Hevesy to the present. Descriptions of
  the following are given: study of cholesterol and arteriosclerosis;
  cobalt labeled vitamin B₁₂ used to study pernicious anemia; history of
  iodine radioisotopes and the thyroid; brain tumor localization;
  determination of body fluid volumes; red cell lifetime; and use of
  radioisotopes for the treatment of various diseases.

  _Medicine_, 20 minutes, sound, color, 1957. Produced by the U. S.
  Information Agency. Four illustrations of the use of radioactive
  materials in diagnosis and therapy are given: exact preoperative
  location of brain tumor; scanning and charting of thyroids; cancer
  therapy research; and the study of blood diseases and hardening of the
  arteries.

  _Radiation Protection in Nuclear Medicine_, 45 minutes, sound, color,
  1962. Produced by the Fordel Films for the Bureau of Medicine and
  Surgery of the U. S. Navy. This semitechnical film demonstrates the
  procedures devised for naval hospitals to protect against the gamma
  radiation emitted from materials used in radiation therapy.

The following films in the Magic of the Atom Series were produced by the
Handel Film Corporation. They are each 12½ minutes long, have sound, and
are in black and white.

  _The Atom and the Doctor_ (1954) shows three applications of
  radioisotopes in medicine: testing for leukemia and other blood
  disorders with radioiron; diagnosis of thyroid conditions with
  radioiodine; and cancer research and therapy with radiogallium.

  _The Atom in the Hospital_ (1961) (available in color and black and
  white) illustrates the following facilities at the City of Hope
  Medical Center in Los Angeles: the stationary cobalt source that is
  used to treat various forms of malignancies; a rotational therapy unit
  called the “cesium ring”, which revolves around the patient and
  focuses its beam on the diseased area; and the total-body irradiation
  chamber for studying the effects of radiation on living things.
  Research with these facilities is explained.

  _Atomic Biology for Medicine_ (1956) explains experiments performed to
  discover effects of radiation on mammals.

  _Atoms for Health_ (1956) outlines two methods of diagnosis and
  treatment possible with radiation: a diagnostic test of the liver, and
  cancer therapy with a radioactive cobalt device. Case histories are
  presented step-by-step.

  _Radiation: Silent Servant of Mankind_ (1956) depicts four uses of
  controlled radiation that can benefit mankind: bombardment of plants
  from a radioactive cobalt source to induce genetic changes for study
  and crop improvement; irradiation of deep-seated tumors with a beam
  from a particle accelerator; therapy of thyroid cancer with
  radioactive iodine; and possibilities for treating brain tumors.




                             PHOTO CREDITS


Cover Courtesy Brookhaven National Laboratory

  Page
  1             General Electric Company
  2, 3, & 4     _Discovery of the Elements._ Mary Elvira Weeks, Journal of
                Chemical Education
  6             Nobel Institute
  12            Chicago Wesley Memorial Hospital (main photo)
  13            Lawrence Radiation Laboratory (LRL)
  14            Brookhaven National Laboratory
  17            LRL
  21            LRL
  22            Los Alamos Scientific Laboratory
  24            LRL
  28            Argonne National Laboratory
  39            Paul V. Harper, M. D.
  41            University of Texas, M. D. Anderson Hospital and Tumor
                Institute

This booklet is one of the “Understanding the Atom” Series. Comments are
invited on this booklet and others in the series; please send them to
the Division of Technical Information, U. S. Atomic Energy Commission,
Washington, D. C. 20545.

Published as part of the AEC’s educational assistance program, the
series includes these titles:

  _Accelerators_
  _Animals in Atomic Research_
  _Atomic Fuel_
  _Atomic Power Safety_
  _Atoms at the Science Fair_
  _Atoms in Agriculture_
  _Atoms, Nature, and Man_
  _Books on Atomic Energy for Adults and Children_
  _Careers in Atomic Energy_
  _Computers_
  _Controlled Nuclear Fusion_
  _Cryogenics, The Uncommon Cold_
  _Direct Conversion of Energy_
  _Fallout From Nuclear Tests_
  _Food Preservation by Irradiation_
  _Genetic Effects of Radiation_
  _Index to the UAS Series_
  _Lasers_
  _Microstructure of Matter_
  _Neutron Activation Analysis_
  _Nondestructive Testing_
  _Nuclear Clocks_
  _Nuclear Energy for Desalting_
  _Nuclear Power and Merchant Shipping_
  _Nuclear Power Plants_
  _Nuclear Propulsion for Space_
  _Nuclear Reactors_
  _Nuclear Terms, A Brief Glossary_
  _Our Atomic World_
  _Plowshare_
  _Plutonium_
  _Power from Radioisotopes_
  _Power Reactors in Small Packages_
  _Radioactive Wastes_
  _Radioisotopes and Life Processes_
  _Radioisotopes in Industry_
  _Radioisotopes in Medicine_
  _SNAP, Nuclear Space Reactors_
  _Sources of Nuclear Fuel_
  _Space Radiation_
  _Spectroscopy_
  _Synthetic Transuranium Elements_
  _The Atom and the Ocean_
  _The Chemistry of the Noble Gases_
  _The Elusive Neutrino_
  _The First Reactor_
  _The Natural Radiation Environment_
  _Whole Body Counters_
  _Your Body and Radiation_

A single copy of any one booklet, or of no more than three different
booklets, may be obtained free by writing to:

           USAEC, P. O. BOX 62, OAK RIDGE, TENNESSEE    37830

Complete sets of the series are available to school and public
librarians, and to teachers who can make them available for reference or
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Students and teachers who need other material on specific aspects of
nuclear science, or references to other reading material, may also write
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exactly, and the use intended.

In all requests, include “Zip Code” in return address.


                Printed in the United States of America
USAEC Division of Technical Information Extension, Oak Ridge, Tennessee




                               FOOTNOTES


[1]The early dangers from use of X rays, due to incomplete understanding
    and inadequate shielding, have now been eliminated.

[2]Gamma rays are high-energy electromagnetic radiation.

[3]Alpha particles are large positively charged particles, identical to
    helium nuclei. For definitions of unfamiliar words see _Nuclear
    Terms, A Brief Glossary_, a companion booklet in this series.

[4]For detailed descriptions of these waves and particles, see _Our
    Atomic World_, a companion booklet in this series.

[5]An equivalent statement is that nuclei of isotopes have the same
    number of protons but different numbers of neutrons.

[6]See Appendix for a description of types of radiation-detection
    instruments.

[7]See _Radioisotopes and Life Processes_, another booklet in this
    series, for a discussion of one area of biomedical research.

[8]A positron is an “antielectron”. It has the mass of an electron but a
    positive charge.

[9]A collimator is a focusing device consisting of a series of slits
    between blocks of shielding material. Consult the Appendix for
    descriptions of other instruments mentioned here.

[10]The superscript m after this isotope indicates an excited state of
    the atom.

[11]As radioactive nuclei disintegrate, they change to other radioactive
    forms—their “daughter” products. Every radioisotope is thus part of
    a chain or series of steps that ends with a stable form.
    Technetium-99^{m} is a daughter product of molybdenum-99; it decays
    by a process known as isomeric transition to a state of lower energy
    and longer half-life.

[12]The curie is the basic unit of radiation intensity. One curie is
    approximately the amount of radioactivity in 1 gram of radium.

[13]See Your Body and Radiation and The Genetic Effects of Radiation,
    other booklets in this series, for detailed explanations of
    radiation effects.

[14]The use of radium is not under AEC control.

[15]One family of measuring instruments is described in
    _Whole Body Counters_,
    another booklet in this series. These are large devices that make
      use of scintillating crystals or liquids.




                            Transcriber’s Notes


--Retained publication information from the printed edition: this eBook
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--Where possible, UTF superscript and subscript numbers are used; some
  e-reader fonts may not support these characters.

--In the text version only, underlined or italicized text is delimited
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End of Project Gutenberg's Radioisotopes in Medicine, by Earl W. Phelan