Joseph G. Hamilton

The Use of Radioactive Tracers in Biology and Medicine1

A very large share of investigative work in the biological sciences has been devoted to the study of the metabolism of organisms ranging in complexity from bacteria to man and embracing the more important members of the plant and animal kingdoms. Until the discovery of artificial radioactivity by Curie and Joliot in 1934 (1), the only method for studying the mechanisms whereby the various elements and compounds essential for life are assimilated, distributed throughout the tissues, converted into other compounds, and finally eliminated, was by a direct chemical approach to these problems. This mode of attack, although very productive of information, suffers from several serious limitations. First, in order to observe the manner by which a living organism metabolizes an element, as, for example, potassium, it is necessary to administer enough so that a detectable increase in the amount in the body will be produced. This axiom applies to most of the elements and compounds that are normal constituents of bio...

A Tracer Study of the Transfer of F18 to Teeth By Topical Application

T HE success of topically applied 2 per cent NaF solutions as a caries preventive agent49 has been tacitly assumed to be related to the uptake of fluoride ions by sound enamel.12 Accordingly, a number of attempts, to measure, by chemical means, the uptake of fluorides by enamel, have been made. Norvold, Inglis, and Armstrong,8 were able to demonstrate an increased percentage of fluoride ions in extracted teeth which were immersed in a 0.2 per cent solution for intervals of 100 to 200 minutes. However, Armstrong and Knutson,2 using teeth of children receiving 2 to 6 clinical applications of a 2.0 per cent solution, found by chemical analysis no increase in the fluoride content of the enamel. They suggested that any increase that might be found would be located in the surface layer of enamel and that it would be of a magnitude small enough to be obscured by measurements performed on the whole enamel. The outer 10 per cent of enamel was analyzed by Syrrist1 who exposed childrens teeth to 2 and 4 per cent NaF solutions for 20 to 40 minutes. It was found that when pooled samples of 10 treated teeth were analyzed and compared to similar samples of untreated teeth, a definite increase in fluorine content was observed. To avoid the problem of analyzing the teeth for fluorine, Straub and Adler10 performed an in vitro study on fragments of enamel in which the solution containing the NaF was analyzed before and after varying lengths of contact with the enamel. An equilibrium between the fluorides of enamel and solution was established in 1 hour at which time the enamel had increased in fluoride content by 3.6 times. Adler, Straub, and Popovies used the same method of analyzing the solution in an in vivo study on human teeth. They were able to show marked decreases in the fluoride content of the solution bathing the teeth when variations in technique were adopted. All of these investigations have had as their goal the determination of whether or not quantitative amounts of fluorine are transferrable to teeth. Such information would be of aid in furthering our understanding of the mechanisms of action of fluoride ions applied in this manner. The chief difficulty in obtaining such data by chemical means lies in the fact that there is no way to distinguish between the fluoride ions already present in a tooth and the small amount added to the enamel by the experimental procedure. The use of radioactive fluorine offers the possibility of circumventing this problem. In addition,

The induction of tumors in the rat by astatine-211.

Exposure of rats to sublethal amounts of At/sup 211/ results in the early appearance of large numbers of mammary tumors, many of them malignant, and in the production of an altered functional state simulating menopause. It is evident that the tumor induction is not yet tested for its association with radiation exposure separately from the endocrine disturbance. (auth)

The Intravenous and Intraduodenal Administration of Radio-Sodium

THE internal use of the radio-active elements was reported by many investigators in this country and abroad within a few years after these substances became available for medical purposes. In 1914, Proescher (1) gave from 50 μgm. to 350 μgm. of radium chloride by vein to more than a score of patients and stated that there were no immediate toxic manifestations to be noted. He stated that marked symptomatic and clinical improvement was observed in patients with arthritis and hypertension. Similar studies were made and conclusions reached by Field (2), Delano (3), Moriarta (4) and Pinch (5). However, these investigators did not make control studies, and their follow-up reports were inadequate. Proescher and Almquist (6) reported the effect of radium given parenterally to a small series of rats and mice. They attempted to evaluate the relation between the amount given and the length of life after injection. They followed the blood counts of all the animals and noted the pathologic changes at the time of deat...

THE METABOLSIM AND TOXICITY OF RADIUM-223 IN RATS

UCRL 8189 UNIVERSITY OF CALIFORNIA THE METABOLISM AND TOXICITY RADIUM-223 IN RATS OF TWO- WEEK LOAN COpy ,Ii This is a library Circulating Copy which may be borrowed for two weeks. For a personal retention copy, call Tech. Info. Diuision, Ext. 5545

The Distribution of Radioisotopes of Some Heavy Metals in the Hat

A summary is presented of data on the biological half times amd the principal deposition sites of 18 heavy metals in rats. Tracer techniques were used in the studies. Data are included on the following elements: Cd, Hg, In, Tl, M, Pb, Nb, Ta, Mo, W, Tc, Re Ru, Os, Rh, Ir, Pd, and Pt. (C.H.)

Excretion of Radio-Sodium Following Intravenous Administration in Man

After the first extensive internal use of naturally radioactive compounds in man by Proescher and others, 1 , 5 Seil, et al., 6 estimated that from 40% to 60% was lost from the body, chiefly through the feces. A progressive diminution in the rate of excretion was indicated by Schlundt and his group, 7 who found that patients retained 4.3% 6 months after administration and 1.9% 6 months later. Sehlundt and Failla 8 found 24 μgm. and 14 μgm. respectively in 2 women 12 years after oral ingestion of radium, with respective coefficients of excretion of .005% and .0025%. Prolonged retention has been reported in many cases of industrial radium poisoning. 9 , 10 Following the announcement by Curie and Joliot 11 of the preparation of an artificial radioactive isotope of nitrogen in 1934, Lawrence and his co-workers 12 produced relatively large amounts of radioactive isotopes of many elements using their magnetic resonance accelerator. Radio-sodium became available for clinical study at the University of California Hospital in the Spring of 1936. It was felt that many of the disadvantages of internal radium therapy could be avoided by the use of radio-sodium, since this latter substance does not tend to become fixed in the body tissues and the duration of its effect is limited by its short half-life of only 14.8 hours. Initial investigations were made of the clinical effect and the rate of excretion of the radio-sodium following its intravenous administration to 2 human leukemic subjects.∗ An approximately isotonic solution of sodium chloride was used in each experiment. Each sample was measured with an electroscope just prior to administration and periodic determinations of the degree of activity of the patients body was carried out. At the same time all the stool and urine samples were collected and their activities measured. The activity of 100 cc. of blood from the second patient was determined. The first patient received 13 mc.e. (milli-Curie equivalents) of radio-sodium and in Fig. 1 are shown the measured and theoretical decay curves in the upper portion of the chart. The theoretical values were computed from the first measurement of the patients activity.

Comparative Deposition of Zr95 in a Reticulo Endothelial Tumor to Normal Tissue in a Human Patient

A test dose of Zr{sup 95} was given to a female patient which had a metastatic reticula endothelial tumor at the distal portion of the left femur. A comparison of the deposition of Zr{sup 95} showed greater uptake 24 hours after administration than any of the normal tissues investigated.