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APPENDIX TV

Radioactive lodine

Excerpts from "Radioactive lodine in the Study of Thyroid Physiology", by
Saul Hertz, M.D., Boston, and Arthur Roberts, Ph.D., Cambridge, Massa-
chusetts. The Journal of the American Medical Association, Vol. 131, No.
2, page 81, May 1946.

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On the basis of a series of animal and clinical experiments using radioactive isotopes of iodine as a tracer in the study of thyroid physiology and iodine metabolism, the treatment of 29 cases of hyperthyroidism with internal irradiation by radioactive iodine was instituted. By careful excretion studies, external counter measurements over the thyroid gland and by planned operations in 2 cases, data were obtained which allow us to construct a formula for a procedure in treatment.

The addition of ordinary iodine therapy after the administration of radio-iodine offers many advantages in the clinical care of these patients and in the economy and safety of the procedure.

By an analysis, over a long period, of both the failures and successes in this series of 29 cases, it is shown that radioactive iodine when given in the dosage range of 5 to 25 millicuries to uniodinized patients with hyperthyroidism possessing goiters of 60 to 75 Gm. is highly effective as a cure of the disease in about 80 per cent of cases. When appreciable activity has been administered and subtotal thyroidectomy is resorted to, myxedema or hypometabolism may be expected to develop in a large fraction of the cases (100 per cent in 5 cases in this series).

Excerpts from "The Treatment of Hyperthyroidism with Radioactive lodine",
by Earle M. Chapman, M.D., and Robley D. Evans, Ph.D., Cambridge, Massa-
chusetts. The Journal of the American Medical Association, Vol. 131, No. 2,

page 86, May 1946. 1. In hyperthyroidism orally administered doses of radioactive iodine, carried in about 1 mg. or less of ordinary iodine, are concentrated largely in the thyroid gland. The beta rays from the radioactive iodine deliver within the thyroid an internal radiation which is physically similar to roentgen radiation. The radiation does in a patient who swallowed 14 millicuries has been calculated as equivalent to approximately 3,490 roentgens, due to the 12-hour isotope.

2. Between May 1943 and March 1945, 22 patients having hyperthyroidism were treated with large doses of radioactive iodine. No other form of therapy was given.

3. Fourteen patients responded well to a single dose of radioactive iodine; 3 were given two doses and 5 were given three doses. Myxedema has followed this treatment in 4 patients. Two patients after treatment with this agent, though improved, still have mild hyperthyroidism.

4. Reactions which resembled roentgen ray sickness were observed in 6 patients following large doses of radioactive iodine. Fibrosis of the thyroid has been observed in biopsy of 2 patients after treatment. 5. Patients who have not responded to other forms of treatment

have been sensitive to iodine or thiouracil have responded well to radioactive iodine. Ordinary iodine is not necessary with radioactive iodine treatment.

6. We believe that therapy with radioactive iodine can be added to the growing list of medical methods for the control of thyrotoxicosis.

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6. Medical Applications

By R. S. Stone

Formerly in charge of Medical Research for Metallurgical Project

of Manhattan District Head of Department of Roentgenology, Medical School, Uni

versity of California J. G. Hamilton

Formerly in charge of Medical Research of University of Cali

fornia for Manhattan District Associate Professor of Medical Physics, University of California

Cancer Therapy With Neutron Rays

The future possibilities of the use of neutrons for therapeutic purposes are somewhat limited in scope. Very energetic neutrons, that is, in the range of energies that can be produced by large cyclotrons, have already been employed to a limited degree in the treatment of various types of malignancies in man. These results, which are essentially preliminary in character, indicate that there is probably no very great superiority of fast neutrons over x-rays for the treatment of cancer. Further investigation is most certainly warranted to establish more definitely the degree of superiority, if

any,

of neutron therapy over the more conventional procedures which employ x-rays.

The fast neutrons produced by fission possess relatively low energies and for this reason it is generally conceded that they have little, if any, therapeutic potentialities for the treatment of cancer.

A possibility does exist that thermal neutrons might conceivably be useful in attacking certain types of malignancies in which the neoplastic tissue has been previously infiltrated with material possessing a high capture cross-section for fission with thermal neutrons. This particular application of nuclear energy for the cancer problem is not particularly hopeful but there is sufficient possibility of success to make at least some preliminary investigation of this situation desirable.

Cancer Therapy With Proton Rays

In this connection the most interesting, and possibly most hopeful, mode of attack of the cancer problem by means of external irradia

tion lies in the use of the extremely high-energy positively charged particles, notably protons, that can be produced in cyclotrons and other devices for the acceleration of such particles to the 100 to 200 million volt range. These positively charged particles, because of the relatively low ionization they produce at the surface of the body and the extremely dense ionization toward the end of their range, present a situation which very strongly warrants a considerable degree of exploration in the near future.

Medical Applications of the Radioactive Materials

A far greater scope of application of the various products of nuclear energy lies in the fact that large quantities of a majority of all the known artificial radioelements can be produced by piles. The applications of these substances to the medical and biological sciences lies in two principal categories, namely, the so-called tracer type of investigation and the therapeutic use of these agents.

The widespread interest in carbon-14 alone is an index of the eagerness with which the availability of this and scores of other radioactive isotopes for use as tracers are now being so enthusiastically anticipated by the biologists and medical research workers. For the first time, the opportunity is now at hand to attack thoroughly an almost infinite number of problems which are of concern to the fundamental mechanisms of life processes. For this purpose, carbon-14 will be the most important of all radioelements that can be produced in the pile, but others such as radioactive hydrogen, sulfur, phosphorus, et cetera, each have startling breadth of application in all of the biological sciences. It should be noted in passing that radioelements, soon to be available from piles, will be of inestimable value to those working in the fields of the agricultural sciences. These research workers will now have placed in their hands a tool which will permit them to attack the problems relating to growth of plants with specific reference to improvement of the fertility of the soil and enhancement of crop yields.

The second phase of the applications of the artificial radioelements to the medical sciences lies in their use as therapeutic agents for the treatment of certain disease processes in man. The possibilities in this direction have as yet been only meagerly explored but already it has been shown that artificial radioelements such as phosphorus have proved useful in the treatment of a few malignant conditions, notably blood disorders such as leukemia and polycythemia vera. Another interesting example has been the employment of radioactive iodine as a successful agent for the treatment of a non-malignant type of thyroid disease, hyperthyroidism, and now recent work in this country

has revealed that radioactive iodine may prove to be of value in the therapy of certain types of thyroid cancer.

Emphasis should be laid not upon the limited progress that has been made to date on the therapeutic application of the artificial radioelements but rather in the implications of things that we can expect to come in the future. The fundamental fact has already been demonstrated that, if a sufficient quantity of a radioactive material can be made to localize in a diseased structure of the body such as the thyroid gland, intense irradiation of that organ will take place without damage to adjoining normal tissues. The widespread availability of adequate quantities of the artificial radioelements will make possible a more rapid and effective search for radioactive compounds which may be localized in malignant tissues by virtue of the fact that the metabolism of cancer cells is, as we already know, different in certain subtle ways from the metabolism of normal cells. No one, of course, can predict when such a search may achieve success but it is obvious that the date of the attainment of this goal will in no small degree be proportional to the availability of the artificial radioelements to qualified research workers in laboratories throughout the world.

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