THE EFFECT OF DIFFERENT DOSE LEVELS OF DEGRADABLE STARCH MICROSPHERES(SPHEREX(R)) ON THE DISTRIBUTION OF A CYTOTOXIC DRUG AFTER REGIONAL ADMINISTRATION TO TUMOR-BEARING RATS

Tumour uptake of a radiolabelled anticancer drug, tauromustine ([C-14] TCNU), was investigated, using two different routes of administration in rats with colon adenocarcinomas implanted in the liver. Intra-arter ial administration produced higher concentrations of the drug and/or i ts metabolites in tumour tissue and lower concentrations in normal tis sue compared to intravenous administration. The investigation of co-in jection of [C-14]TCNU intra-arterially with degradable starch microsph eres (DSM) indicated that a high dose of DSM (30 mg/kg) resulted in a high concentration of radioactivity in normal liver tissue, and in adj acent organs. This unfavourable pattern was not observed with the low dose of DSM (12.5 mg/kg), which produced a significant increase in tum our uptake. The results demonstrate the efficacy of partial vascular b lockade, as elicited by the low dose of DSM. This regime caused [C-14] TCNU to be preferentially retained in the active peripheral regions of the tumour.