Combined therapeutic efficacy of188Re-liposomes and sorafenib in an experimental colorectal cancer liver metastasis model by intrasplenic injection of C26-lucmurine colon cancer cells.
Rhenium-188 (188Re) displays abundant intermediate energy β emission and possesses a physical half-life of 16.9 h. Sorafenib is an orally available multikinase inhibitor that targets Raf kinases and vascular endothelial growth factor receptors (VEGFRs). Sorafenib has demonstrated preclinical and clinical activity against several types of tumors, such as renal cell and colorectal carcinoma. In this study, we investigated the efficacy of radiotherapeutics of188Re-liposomes combined with sorafenib in a C26-lucmetastatic colorectal liver tumour mouse model. Liver metastases were established by intrasplenic injection of C26-lucmurine colon cancer cells. Based on the results of the toxicity assessment, an administration dose of 80% the maximum tolerated dose was selected.188Re-liposomes were administered on day 1, when metastases of several hundred micrometers in diameter were observed. In the combination therapy group, 10 mg/kg sorafenib (co-developed and co-marketed by Bayer and Onyx Pharmaceuticals as Nexavar) was administered every other day for 1 week and the survival of mice was assessed. The tumor growth was more significantly inhibited in the188Re-liposome plus sorafenib group compared with the188Re-liposome alone, sorafenib alone and untreated normal saline groups (P=0.0000). Furthermore,188Re-liposomes combined with sorafenib achieved higher survival rates compared with the188Re-liposome alone, sorafenib alone and untreated normal saline groups (P=0.0000). These results support the use of combined radio-chemotherapy with188Re-liposomes plus sorafenib as a viable treatment option in the adjuvant setting for liver metastases of colorectal cancer.
Institute of Nuclear Energy Research, Lungtan, Taoyuan;
Ya-Jen
YJ
Chang
Institute of Nuclear Energy Research, Lungtan, Taoyuan;
Wei-Hsin
WH
Hsu
Institute of Nuclear Energy Research, Lungtan, Taoyuan;
Chih-Hsien
CH
Chang
Cancer Center, Taipei Veterans General Hospital;
Keng-Li
KL
Lan
National Health Research Institutes, Taipei, Taiwan, R.O.C.
Gann
G
Ting
Institute of Nuclear Energy Research, Lungtan, Taoyuan;
Te-Wei
TW
Lee
colon cancer; liposomes; liver metastasis; radiotherapy; rhenium-188