TY - JOUR T1 - Enhanced therapeutic efficacy of combined Sorafenib and 3-bromopyruvate in murine orthotopic liver cancer assessed by bioluminescence image JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 1331 LP - 1331 VL - 57 IS - supplement 2 AU - Kyungmin Kim AU - Juri Na AU - Hyewon Youn AU - Su Jong Yu AU - Keon Wook Kang AU - June-Key Chung Y1 - 2016/05/01 UR - http://jnm.snmjournals.org/content/57/supplement_2/1331.abstract N2 - 1331Objectives Hepatocellular carcinoma (HCC) has been treated with surgical resection and chemotherapy. Sorafenib is the first multikinase inhibitor for the treatment of HCC. Sorafenib in combination with other agents has currently been suggested and there is a need for imaging modality to monitor the therapeutic effect. Using luminescent imaging, we visualized therapeutic effect of combined sorafenib and 3-BrPA in murine orthotopic liver cancer.Methods Tumor bearing mouse models were established in both subcutaneous and orthotopic xenografts. For subcutaneous model, human HCC cell line, SNU-761 cells were subcutaneously injected. About 2 weeks later, mice were randomized into 4 groups; control, sorafenib, 3-BrPA, combination of those drugs when tumor size became more than 55mm3. Drugs (sorafenib: 1.25mg/kg/day, 3-BrPA: 1mg/kg/day) were intraperitoneally injected every 5 days for 3 weeks. Tumor size was measured once a week. For orthotopic model, SNU-761 cells were stably transfected with luciferase gene for bioluminescence imaging. Abdominal region of Balb/c-nu mouse was horizontally resected and SNU761-luc cells were injected to the liver. We put the liver into the original site and stitched the resected part. Six days later, mice were randomized into the 4 groups when the luciferase signals became more than 1x106 photon/sec/cm2/sr. Drugs were intraperitoneally injected every 5 days for 4 weeks. Bioluminescence images were taken once a week.Results In subcutaneous mouse models, tumor grows slowly in the order of control, sorafenib, 3-BrPA, combination of sorafenib and 3-BrPA groups. After 21 days of treatment, tumor size of sorafenib, 3-BrPA and combination of sorafenib and 3-BrPA treated group were reduced to 86.26%, 50.1% and 39.29% of controls, respectively. SNU761-luc cell line was established and luciferase signal was in concordance with the number of viable cancer cell (R2=0.9978). In orthotopic mouse models, tumor grows slowly in the order of control, sorafenib, 3-BrPA, combination of sorafenib and 3-BrPA groups. After 28 days of treatment, bioluminescence signals of sorafenib, 3-BrPA and combination of sorafenib and 3-BrPA groups were reduced to 85.12%, 36.57% and 19.86% of controls, respectively. Sizes of tumor were measured after autopsy, and they were significantly different among 4 groups similar to the imaging results. Compared the synergistic effect of combination of sorafenib and 3-BrPA, we found significant reduction of tumor size in orthotopic models.Conclusions We can visualize the synergistic effect of combined sorafenib and 3-BrPA by optical assessment. This synergistic effect was prominent in orthotopic models. Because microenvironmental factors can influence the therapy result, we prefer orthotopic model rather to conventional subcutaneous model. ER -