Read Ebook: Radioisotopes in Medicine by Phelan Earl W

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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 . 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 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.

Still another common measurement using ??Cr-labeled red blood cells is the determination of the amount and location of bleeding from the gastrointestinal tract . 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 ??Cr-labeled blood serum. The serum is treated with CrCl? 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 ??Cr level in the intestinal excretions is high, and this alerts the doctor to apply remedial measures.

Cobalt-60

If the B?? is labeled with radioactive cobalt, its passage into the blood stream may be observed by several different methods. The simplest is to give the B?? 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 ??Co 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.

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 .

One of the common diagnostic procedures for determining thyroid function, therefore, is to measure the percentage of an administered dose of ???I 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.

To determine local activity in small portions of the thyroid, an automatic scanner is used. A collimator shields the detector 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.

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 , 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 ???I 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 ???I 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.

Human serum albumin labeled with ???I 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.

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, ??Fe, 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.

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 ??P 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 ??P 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 ??Na in some measurements of the blood and other fluids. The figure illustrates this technique. A sample of ??NaCl 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.

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.

Technetium-99^

Because of its short half-life of six hours, technetium-99^ 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. 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.

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" 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.

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 was first discovered, heavy water 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 . 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 has been produced in abundance. Its oxide, tritiated water , 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 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.

Activation Analysis

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 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.

??Co 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.

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