LIVER METASTASES FROM COLORECTAL-CANCER - DRUG-DELIVERY WITH LIPOSOME-ENCAPSULATED DOXORUBICIN

PURPOSE: To evaluate the intratumoral distribution of liposome-encapsu lated doxorubicin. MATERIALS AND METHODS: Tumor-bearing livers of 24 m ice were studied with in vivo fluorescence and electron microscopy aft er injection of liposomal doxorubicin in the hepatic artery, portal ve in, or tail vein. Distribution and uptake of liposomes and doxorubicin in tumors were compared at 5, 30, and 60 minutes after injection. In vitro evaluation of uptake of doxorubicin in Kupffer cells and in huma n colorectal cancer cells incubated under normoxic and hypoxic conditi ons for 5, 30, and 60 minutes was performed with fluorescence microsco py. RESULTS: Doxorubicin autofluorescence was seen in tumors 30 minute s after intraarterial and intraportal injection and was statistically significantly greater at 60 minutes (P < .001). Liposomes were observe d in small tumors (diameter < 300 mu m) and were trapped in Kupffer ce lls around larger, hypovascular tumors. Electron microscopy findings c onfirmed intracytoplasmic, perinuclear uptake of liposomes in tumor ce lls. In vitro, a higher proportion of doxorubicin was seen in cancer c ells (92%) than in Kupffer cells (75%) after 60 minutes incubation. CO NCLUSION: Liposomal doxorubicin can be reliably delivered to liver met astases via the hepatic artery, eliminating need for tumor embolizatio n. Further evaluation is warranted, and the drug may be useful for tre ating patients with unresectable liver metastases.