Regional targeting of bisantrene by directed intravascular precipitation

Targeting of anticancer drugs to specific organs by directed intravascular precipitation was studied in calves using 9-10 anthracenedicarboxyaldehyde bis [(4,5-dihydro-lH-imidazol-2-yl) hydrazone] dihydrochloride (Bisantrene), a clinically active anticancer drug with limited solubility at physiological pH. Rapid injection of Bisantrene in solution at pH 4.5 into the internal iliac artery resulted in concentrations of drug in the urinary bladder wall supplied by the artery that were more than 1000 times those in the same tissue following injection of the same dose of drug IV, the route of administration used clinically. Localization of the orange fluorescent drug to the ipsilateral bladder wall was easily seen. Fluorescence microscopy revealed deposits of drug along the walls of the arteriolar and capillary bed supplied by the artery into which it had been injected. Concentrations of drug in the systemic circulation and in tissues not supplied by the internal iliac artery used for drug injection were lower after intraarterial (IA) drug administration than after IV administration. Pathological studies of the tissues of calves sacrificed at intervals up to four weeks following rapid injection into the internal iliac artery of the same doses of Bisantrene used IV in cancer patients did not reveal evidence of extensive cytotoxicity to the infused organs.