Prediction of the Effective Radioprotective Dose of WR-2721 in Humans through an Interspecies Tissue Distribution Study

On the basis of earlier tissue distribution data, obtained in mice and rats, we proposed that the tissue distribution of intravenously injected S-2-[3-aminopropylamino]-ethyl-phosphorothioic acid (WR-2721) was more closely correlated with the injected dose per unit surface area than it was with the...

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Bibliographic Details
Published in:Radiation research 1976-04, Vol.66 (1), p.100-105
Main Authors: Washburn, L. C., Rafter, J. J., Hayes, R. L.
Format: Article
Language:English
Subjects:
Animals
Body Surface Area
Body tissues
Body Weight
Dogs
Dosage
Female
Humans
Male
Mice
Organothiophosphorus Compounds - administration & dosage
Organothiophosphorus Compounds - therapeutic use
Rabbits
Radiation-Protective Agents - administration & dosage
Radiation-Protective Agents - therapeutic use
Radiotherapy
Rats
Space life sciences
Surface areas
Tissue distribution
Tumors
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Summary:On the basis of earlier tissue distribution data, obtained in mice and rats, we proposed that the tissue distribution of intravenously injected S-2-[3-aminopropylamino]-ethyl-phosphorothioic acid (WR-2721) was more closely correlated with the injected dose per unit surface area than it was with the injected dose per unit body weight. To test this proposal, we have compared the tissue distribution of 35 S-labeled WR-2721 at 15 and 30 min after intravenous injection in mice, rats, rabbits, and dogs. The results of this study demonstrate that the tissue distribution is not a strict function of either the body weight or the surface area, but rather falls intermediate to the predictions of these parameters. By extrapolation, this observation would predict that a dose of 20 mg of WR-2721 per kilogram of body weight would provide humans with the same amount of protection that 100 mg/kg provides the mouse, i.e., a 50-80% increase in radiation resistance.
ISSN:0033-7587
1938-5404
DOI:10.2307/3574359