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]