Radioisotopes in Medicine :: THERAPY A Successful Case

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.

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“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.

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).

(1) A lead shutter shields the patient from reactor neutrons.

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

(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.

(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).

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Survival of polycythemia vera patients after ³²P therapy.

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.

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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.

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.

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.

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.

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