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The development of radioimmunotherapy has provided an impressive alternative approach in improving trastuzumab therapy. However, the mechanisms of trastuzumab and radiation treatment combined to increase therapeutic efficacy are poorly understood. Here, we try to examine the efficacy of cytotoxicity and apoptosis induction for (188)Re-HYNIC-trastuzumab in cancer cell lines with various levels of Her2.Fluorescence flow cytometry was used to detect the alterations of apoptosis induction after (188)Re-HYNIC-trastuzumab treatment in two breast cancer cell lines with different levels of HER2 (BT-474 and MCF-7) and a colorectal carcinoma cell line (HT-29) for control.Our results indicated that (188)Re-HYNIC-trastuzumab led to cell death of breast cancer cells specifically in HER2 level-dependent and radioactivity dose-dependent fashions. In BT-474 cells, 370 kBq/ml of (188)Re-HYNIC-trastuzumab enhanced the cytotoxicity to a level nearly 100-fold that of trastuzumab-alone treatment. The results also revealed that the mitochondria-dependent pathway attenuated irradiation-induced apoptosis in HER2-expressing breast cancer cells after (188)Re-HYNIC-trastuzumab treatment. In contrast, only after 48 h of (188)Re-HYNIC-trastuzumab treatment, BT-474 cells exhibited typical apoptotic changes, including exposure of phospholipid phosphatidylserine on the cell surface, or fragmented DNA formation, in a radioactivity dose-dependent manner.Briefly, our study demonstrates that (188)Re-labeled HYNIC-trastuzumab not only enhances cell death in a radioactivity dose-dependent fashion, but may also prolong the effects of apoptosis involved with the mitochondria-dependent pathway in HER2-overexpressing breast cancer cells. It is possible that the (188)Re-HYNIC-trastuzumab treatment induced a second round of apoptosis to prolong the effects of cell kill in these cancer cells. These data revealed that (188)Re-HYNIC-trastuzumab has the potential for use as a therapeutic radiopharmaceutical agent in HER2-overexpressing breast cancer cell treatment.

In our recent study, we developed a new radiopharmaceutical (Re-188 MN-16ET lipiodol) with encouraging results for the treatment of liver malignancy. In this study, we further evaluated the therapeutic efficacy of this radiopharmaceutical by measuring tumor response and survival times in rats with liver tumors after intra-hepatic arterial injection of Re-188 MN-16ET lipiodol.Twelve male rats bearing hepatic tumors were divided into three groups. Group 1 received an intra-hepatic arterial injection of 18.5 MBq Re-188 MN-16ET lipiodol; Group 2 received lipiodol and Group 3 received normal saline. Tumor size was measured by liver sonography before injection, at 2, 4, and 8 weeks after injection. Survival time and response rate were calculated.All rats showed good response and survived over 60 days in Group 1 while all rats showed poor response in Group 2 and Group 3 with only 25 % of rats in Group 2 and none (0 %) in Group 3 survived over 60 days. The p value was 0.0067 between Group 1 and Group 3; 0.04 between Group 1 and Group 2; and 0.034 between Group 2 and Group 3.Re-188 MN-16ET lipiodol has good potential for the treatment of hepatoma.

Purpose: Several studies have reported significant renal toxicity after the use of a high dose of90Y-DOTATOC. Thus, renal protection is necessary in treatments with90Y-DOTA Tyr3-octroetide (DOTATOC). The infusion of certain positively charged amino acids has been shown to effectively reduce renal uptake of DOTATOC. In this study, we compared the effectiveness of three kinds of amino acids, D-lysine (lysine),L-arginine (arginine) and histidine, on renal protection in healthy rats and tried to determine which one was the most effective.Methods: Twenty SD healthy male rats were divided into 4 groups: lysine, histidine, arginine, and control. The rats were injected with a dose of 400 mg/kg of amono acid or 2 ml of phosphate-buffered saline (PBS) (as control) intraperitoneally. All rats were sacrificed at 4 hrs after the injection of 1 MBq111In-DOTATOC. Samples of the kidney were taken and weighed carefully. The counts of radioactivity were measured by a gamma counter and renal concentrations were calculated and expressed as percent injected dose per gram (% ID/g).Results: The renal uptake of111In-DOTATOC was significantly lower for all three kinds of amino acids when compared to the control group. The renal uptake of111In-DOTATOC in the lysine group was significantly lower than those in the histidine and arginine groups. The renal uptake of111In-DOTATOC in the histidine group was lower than that in the arginine group, but no statistical difference was noted.Conclusion: Among these three amino acids, lysine had the best reduction rate of renal uptake of DOTATOC. Histidine was more effective than arginine but no statistical difference was noted.