Betty Rosoff

Metabolism of Zinc-65 in Man

In view of the importance of zinc in many enzyme systems, and of the fact that zinc is an essential trace element in the human body, a study of the excretion, retention, and tissue distribution of Zn65 in man was performed. Zinc-65 is also a neutron-induced radionuclide and is, therefore, potentially an internal radiation hazard. The dose from Zn65 is a function of the y-particle distribution and turnover in the body. The tissue distribution and excretion of Zn65 have been investigated in animals (1, 2), and more recently these studies have been extended to man (3, 4). In the present investigation the blood levels, excretions, and tissue distribution of Zn65 in man were also related to the retention of Zn65 in the body as determined by the whole-body counting technique.

Metabolism of the chelating agent diethylenetriamine pentaacetic acid (C14DTPA) in man.

Summary 1. Intravenously injected C14-DTPA in man is quantitatively excreted in urine in 24 hours. 2. Following oral ingestion of C14DTPA, the major portion of the chelate passes unabsorbed through the intestine (90–100%). However, the presence of the C14 chelate in urine is evidence for absorption of some, although small, amounts of the chelating agents. 3. The metabolism of DTPA was shown to be similar to that of EDTA.

Distribution and excretion of radioactive rare-earth compounds in mice☆

Abstract The distribution and excretion of radioactive scandium, yttrium, lanthanum and samarium, intravenously administered to mice in ionic and chelated form, are described. The strong rare-earth chelates (ScEDTA and YEDTA) are well excreted and very little is retained in the tissues. The weak and intermediate chellargely deposited in liver and spleen, and the chelates with intermediate stability (YNTA, ScNTA and SmEDTA) show relatively high concentration in bone. A possible explanation for the difference in tissue distribution of the various rare-earths on the basis of colloidal aggregates, chelate stability, and protein binding is suggested.

I. Cesium-137 Metabolism in Man'

The study of the metabolism and distribution of cesium-137 is of particular interest at present because it is a biologically important fission product present in radioactive fallout. Animal experiments have shows species differences in the excretion patterns of parenterally and orally administered Cs137. For example, in rats and rabbits the primary route of excretion is via the kidney, whereas in cows and sheep most of the cesium is excreted in the feces (1-3). In sheep, 50% to 80% of orally ingested Cs137 was found to be absorbed (3). Tissue distribution studies in animals have shown that the largest concentration of cesium per gram of wet tissue is found in muscle (1-3). Previous investigations of cesium in man have been primarily concerned with the measurement of the levels of fallout-produced Cs137 in various population groups (4). Recently, with the development of total-body counters, it has also been possible to measure the biological half-life of Cs137 in man (5, 6). The results obtained with these measurements are discussed in Part II of this presentation. This report describes a study of the excretion and distribution of Cs137 man, after both oral and intravenous administration of tracer doses of this isotope. Attempts to increase the excretion rate of Cs137 by various chemical agents are also described.

Metabolism of scandium-46 in man☆

Abstract The metabolism, tissue distribution and biological turnover of radioactive chelated scandium were determined in man. When administered intravenously as the weak chelate Sc46 NTA (nitrilotriacetate), Sc46 disappeared very slowly from the vascular space; it was excreted principally via the intestine. When Sc46 was administered as the strong chelate of ethylene-diaminetetraacetic acid, EDTA, or of diethylenetriaminepentaacetic acid, DTPA, the plasma level of Sc46 decreased rapidly and urinary excretion was high, up to 82 percent of the dose being excreted in 24 hr. The concentration of Sc46 in various tissues determined 5,6 and 7 months after the administration of Sc46 NTA showed that uptake was highest in spleen. Evidence is presented which suggests that the high body retention of Sc46 NTA may be due to the formation of colloidal aggregates and to binding of scandium to proteins. The biological half-life of Sc46 NTA determined with the whole-body counter and computer analysis was 1300 days in one patient and 1557 days in another.

Interaction of yttrium compounds with serum and serum constituents in vitro

Abstract A simple method for determining the relative metal-binding strength of chelating agents in physiological media has been proposed and the nature of yttrium chelate interaction with serum has been studied. Filterability of yttrium from serum and serum filtrate was found to be related to the stability (log K 1 ) of the yttrium chelate. The pressure filtration data correspond also with animal and human excretion data obtained in our laboratory. The experiments with serum filtrate show that the diffusible serum components play a role in these yttrium interactions. The yttrium interaction with an isolated serum protein, albumin, was studied by the method of equilibrium dialysis. The moles of yttrium bound per mole of albumin increased as the metal-ion concentration was increased and the binding was found to be reversible, indicating that this is a multiple equilibrium reaction. The yttrium-albumin binding was affected by changes in pH and temperature.

Binding of rare earths to serum proteins and DNA

Abstract In order to investigate further the physiological behavior of rare earths and rare earth chelates, studies of the binding of 46Sc, 91Y, and 140La to serum proteins and to nucleic acids were performed using the methods of equilibrium dialysis and ultrafiltration. The binding of lanthanum and yttrium as the chlorides to α-globulin increased as the free rare earth concentration increased. When scandium and lanthanum were chelated in nitrilotriacetate (NTA) the binding to α-globulin was considerably less and there was no binding to albumin. The binding of 46Sc chelated to ethylenediamine di(O-hydroxyphenylacetate) (EDDHA) was five times greater than of 46Sc chloride. When the free scandium concentration was increased, the moles bound per mole of protein increased proportionally and the binding was reversible. Scandium was 100% filterable from a mixture of human serum and from the scandium chelates with high stability constants scandium diethylenetriaminepentaacetate (ScDTPA), scandium ethylenediaminetetraacetate (ScEDTA) and scandium cyclohexane trans-1, 2-diaminetetraacetate (ScCDTA) respectively. In contrast, only 2% of the scandium was filterable when scandium nitrilotriacetate, a scandium chelate of low stability constant, was used. Both yttrium and lanthanum have been shown to bind to DNA and increasing the rare earth concentrations resulted in an increase of the moles of yttrium or lanthanum bound per mole of DNA. An analysis of the lanthanum-DNA binding suggests that there are multiple binding sites for this rare earth on the DNA molecule.

Tissue distribution of zinc-65 in tumour tissue and normal tissue in man.

ZINC is a trace metal of physiological importance which is widely distributed in many enzyme systems. Changes in the activity of certain enzymes have been reported in normal and tumour tissues of tumour-bearing animals1 and of man2, and in the serum of patients with neoplastic diseases3–7. Since the activity of some enzymes depends on the presence of specific trace metals, cellular derangement resulting in neoplasia may be linked with changes in trace metal concentration. Differences in zinc concentration in normal and tumour tissue in experimental animals and in man have been previously reported8–15.

Effect of chelating agents on the removal of zinc-65 in man.

AbstractThe chelating agents ethylenediaminetetraacetic acid, EDTA, and diethylenetriaminepentaacetic acid, DTPA, were both effective in removing zinc-65 from man and, in most instances, DTPA appeared to be more effective than EDTA. Considerable enhancement in urinary 65Zn excretion could be induced

LONG-TERM Cs

In order to assess the radiation hazard of the fission product Cs/sup 137/, it is necessary to determine its long-term turnover rate in man. Results are reported from a longterm study of Cs/sup 137/ made on five patients. Measurements of whole-body retention were made with the Brookhaven whole-body counter. It has been found that the technique of radiochemical analysis of excreta is of limited sensitivity for determining whole-body retention at very long periods of time after isotope administration. In order to assay the radiation hazard, it is further necessary to estimate the retention over the normal life span of man on the basis of the data obtained. Thus a mathematical model must be developed from which long-term extrapolations can be made. Data analysis was carried out with the use of a computer in order to determine the parameters of the mathematical functions that best describe these data. (auth)