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Chlorpromazine Distribution in Hamsters and Mice Bearing Transplantable Melanoma¹

Brookhaven National Laboratory, Associated Universities, Inc., Upton, New York 11973 [R. G. F., D. G., K. P. W., S. P., H. L. A., P. S., S. J. H., A. B. B.], and Department of Psychiatry and Behavioral Science, Stony Brook University, Stony Brook, New York 11794 [I. F., W. P. M.]

Chlorpromazine (CPZ) distribution was measured in tissues of Syrian golden hamsters bearing Greene melanoma and in BALB/c mice bearing Harding-Passey melanoma. Distribution was evaluated as a function of time (0.5 to 14 days) and as a function of single and multiple doses (up to five) of from 5 to 50 mg CPZ per kg body weight. Routes of administration (i.p., i.v., p.o.) were compared. The physiological behavior of CPZ is of interest as it is used extensively as a tranquilizing drug (Thorazine). Further, since CPZ binds to the pigment melanin, the possibility exists of using CPZ to transport diagnostic or therapeutic agents to melanoma. It was found that, at 2 days postinjection, tumor/tissue concentration ratios exceeded 10 for metabolizing organs, such as liver, and 100 for "background" tissues, such as blood and muscle. Absolute concentrations of CPZ in tumor exceeding 100 µg CPZ per g tumor were obtained with both single and multiple doses. This selective high concentration in tumor would make CPZ an ideal vehicle for the transport of boron to tumor for use in neutron capture therapy via the ¹⁰B(n,)⁷Li reaction.

¹ Work supported by National Cancer Institute Grant R01-CA22749 and United States Department of Energy Contract DE-AC02-76CH00016.

² To whom requests for reprints should be addressed, at Medical Dept., Brookhaven National Laboratory, Upton, N. Y. 11973.

Received 3/30/81. Accepted 10/27/81.