The effect of different dose levels of degradable starch microspheres (Spherex) on the distribution of a cytotoxic drug after regional administration to tumour-bearing rats.
Tumour uptake of a radiolabelled anticancer drug, tauromustine ([14C]TCNU), was investigated, using two different routes of administration in rats with colon adenocarcinomas implanted in the liver. Intra-arterial administration produced higher concentrations of the drug and/or its metabolites in tumour tissue and lower concentrations in normal tissue compared to intravenous administration. The investigation of co-injection of [14C]TCNU intra-arterially with degradable starch microspheres (DSM) indicated that a high dose of DSM (30 mg/kg) resulted in a high concentration of radioactivity in normal liver tissue, and in adjacent organs. This unfavourable pattern was not observed with the low dose of DSM (12.5 mg/kg), which produced a significant increase in tumour uptake. The results demonstrate the efficacy of partial vascular blockade, as elicited by the low dose of DSM. This regime caused [14C]TCNU to be preferentially retained in the active peripheral regions of the tumour.
D000230:Adenocarcinoma / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002250:Carbon Radioisotopes; D003110:Colonic Neoplasms / Q000378:metabolism*; D007269:Injections, Intra-Arterial; D007275:Injections, Intravenous; D008297:Male; D008863:Microspheres; D009368:Neoplasm Transplantation; D009607:Nitrosourea Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D013654:Taurine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D013997:Time Factors; D014018:Tissue Distribution
D000970:Antineoplastic Agents; D002250:Carbon Radioisotopes; D009607:Nitrosourea Compounds; D013654:Taurine; C052991:1-(2-chloroethyl)-3-(2-(dimethylaminosulfonyl)ethyl)-1-nitrosourea