627 ENHANCEMENT OF OSTEOCLASTOGENIC ACTIVITY IN OSTEOLYTIC PROSTATE CANCER CELLS BY PHYSICAL CONTACT WITH OSTEOBLASTS

INTRODUCTION AND OBJECTIVES: Low-temperature sensitive liposomes (LTSLs) release their encapsulated drug into targeted tissue when activated by a source of hyperthermia. The efficacy of an LTSL formulation of docetaxel (DOC) or doxorubicin (DOX) was compared against prostate cancer in a xenograft mouse model. METHODS: Under an approved IACUC protocol, Luciferase transfected human prostate PC-3M-luciferase cells were inoculated (3 10 6 cells) subcutaneously in the right hind leg of 8 wk old female athymic nude mice. When tumors reached a volume of 200–300 mm 3, mice were randomized to receive one intravenous injection of saline, Stealth liposomal DOX (5 mg/kg), LTSL DOX (5 mg/kg), or LTSL DOC (15 mg/kg), with or without hyperthermia treatment (LTSL DOX and LTSL DOC were supplied by Celsion Corp., Columbia, MD). Mice undergoing hyperthermia treatment were anesthetized and stabilized in a holder that allowed for only the leg with tumor to be heated to 41–42C that triggered LTSL drug release. Mice were monitored daily for tumor volume and body weight. Study end-points included growth of tumor to 5x the initial treatment volume or monitoring of survival for 60 days. RESULTS: The LTSL DOC delayed tumor growth longer (20 days) than DOX (7 days) or LTSL DOX (9 days) with hyperthermia (P 0.05). Mice treated with LTSL DOC and hyperthermia survived longest (60 days) compared to all other mice (range 6–8 days, P 0.05). LTSL in the setting of hyperthermia demonstrated complete regression of tumor in 57% of mice. CONCLUSIONS: LTSL DOC with hyperthermia delayed tumor growth more than all other treatments. Survival studies suggest LTSL DOC is a more effective temperature sensitive delivery system against PC-3M prostate tumors.