Biodistribution of NX211, liposomal lurtotecan, in tumor-bearing mice

Prolonging tumor exposure to topoisomerase I inhibitors has been correlated to enhance the efficacy of those agents. Lurtotecan, a water-soluble camptothecin analog, was formulated as a liposomal drug, NX211, to enhance the delivery of drug to tumors. Tumor-bearing mice were treated with either [C-14]NX211 containing [C-14]lurtotecan, [H-3]NX211 containing [H-3]phosphatidylcholine or [C-14]lurtotecan, euthanized at selected times post-injection, and tissues, plasma, urine and feces were collected. These studies demonstrated that KB tumors of [C-14]NX211-treated mice had approximately 70-fold greater concentrations of [C-14]lurtotecan at 24 h, respectively, compared to concentrations of [C-14]lurtotecan of the KB tumors of [C-14]lurtotecan-treated mice. The area under curve (AUC) from 0 to 48 h of [C-14]lurtotecan for the KB tumors of [C-14]NX211-treated animals was over 17-fold greater than the AUC of [C-14]lurtotecan for the tumors of [C-14]lurtotecan-treated animals. Treatment with [H-3]NX211 demonstrated that the lipid component continually accumulated over 24 h in the tissues. HPLC analysis of extracted material from tumors of [C-14]NX211-treated mice showed that more than 95% of the radioactive material was intact [C-14]lurtotecan. These findings are one of the keys justifying the development of a liposomal formulation of lurtotecan, which has the intent to increase tumor exposure and increase antitumor efficacy. [(C) 2001 Lippincott Williams & Wilkins].