ailed Distribution of NK012, an SN-38–Incorporating elle, in the Liver and Its Potent Antitumor Effects

nloaded pose: To clarify and compare the antitumor effects and specific biodistribution of NK012, an –incorporating polymeric micelle, in mice bearing multiple liver metastases of human colon cancer cells with irinotecan hydrochloride (CPT-11). erimental Design: The maximum tolerable dose of NK012 (30 mg/kg) or CPT-11 (66.7 mg/kg) v. administered three times every 4 days to mice bearing metastases to the liver colonized 7 days e portal administration of HT-29 cells (n = 6). In vivo antitumor effects were evaluated by bioluminesimaging and histopathologic examination. Drug biodistribution was analyzed by high-performance chromatography and fluorescence microscopy (n = 3). ults: NK012 eradicated the liver metastases and produced a significant longer survival rate than 1 (P = 0.0006). High-performance liquid chromatography showed the prolonged distribution of 2 and free SN-38 released from NK012 in the tumors, liver, and spleen for weeks after NK012 adtration. On the other hand, the accumulation levels of CPT-11 and free SN-38 converted fromCPT-11 y decreased within 1 day after CPT-11 administration. In the liver metastases, fluorescence microsnd immunohistochemistry showed that administered NK012 was distributed mainly adjacent to tuessels after 1 day. As for the normal liver, NK012was distributed in Kupffer cells instead of hepatocytes least 7 days after administration. clusion: This study suggests that NK012 is strongly effective against liver metastases and does not Con damage the liver despite the long retention time of NK012 in Kupffer cells. Clin Cancer Res; 16(19); 4822–31.