title: Biodistribution of NX211, liposomal lurtotecan, in tumor-bearing mice.
abstract: 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 [14C]NX211 containing [14C]lurtotecan, [3H]NX211 containing [3H]phosphatidylcholine or [14C]lurtotecan, euthanized at selected times post-injection, and tissues, plasma, urine and feces were collected. These studies demonstrated that KB tumors of [14C]NX211-treated mice had approximately 70-fold greater concentrations of [14C]lurtotecan at 24 h, respectively, compared to concentrations of [14C]lurtotecan of the KB tumors of [14C]lurtotecan-treated mice. The area under curve (AUC) from 0 to 48 h of [14C]lurtotecan for the KB tumors of [14C]NX211-treated animals was over 17-fold greater than the AUC of [14C]lurtotecan for the tumors of [14C]lurtotecan-treated animals. Treatment with [3H]NX211 demonstrated that the lipid component continually accumulated over 24 h in the tissues. HPLC analysis of extracted material from tumors of [14C]NX211-treated mice showed that more than 95% of the radioactive material was intact [14C]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.
authors: Gilead Sciences, Inc, 2860 Wilderness Place, Boulder, CO 80301, USA. jdesjardins@gilead.com
authors: J P
authors: JP
authors: Desjardins
authors: E A
authors: EA
authors: Abbott
authors: D L
authors: DL
authors: Emerson
authors: B E
authors: BE
authors: Tomkinson
authors: J D
authors: JD
authors: Leray
authors: E N
authors: EN
authors: Brown
authors: M
authors: M
authors: Hamilton
authors: L
authors: L
authors: Dihel
authors: M
authors: M
authors: Ptaszynski
authors: R A
authors: RA
authors: Bendele
authors: F C
authors: FC
authors: Richardson
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D008081:Liposomes; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: D000970:Antineoplastic Agents; D008081:Liposomes; C091719:lurtotecan; D002166:Camptothecin