Radiolabeled Anti-Adenosine Triphosphate Synthase Monoclonal Antibody as a Theragnostic Agent Targeting Angiogenesis.

INTRODUCTION: The potential of a radioiodine-labeled, anti-adenosine triphosphate synthase monoclonal antibody (ATPS mAb) as a theragnostic agent for simultaneous cancer imaging and treatment was evaluated. METHODS: Adenosine triphosphate synthase monoclonal antibody was labeled with radioiodine, then radiotracer uptake was measured in 6 different cancer cell lines. In vivo biodistribution was evaluated 24 and 48 hours after intravenous injection of 125I-ATPS mAb into MKN-45 tumor-bearing mice (n = 3). For radioimmunotherapy, 18.5 MBq 131I-ATPS mAb (n = 7), isotype immunoglobulin G (IgG) (n = 6), and vehicle (n = 6) were injected into MKN-45 tumor-bearing mice for 4 weeks, and tumor volume and percentage of tumor growth inhibition (TGI) were compared each week. RESULTS: MKN-45 cells showed the highest in vitro cellular binding after 4 hours (0.00324 ± 0.00013%/µg), which was significantly inhibited by unlabeled ATPS mAb at concentrations of greater than 0.4 µM. The in vitro retention rate of 125I-ATPS mAb in MKN-45 cells was 64.1% ± 1.0% at 60 minutes. The highest tumor uptake of 125I-ATPS mAb in MKN-45 tumor-bearing mice was achieved 24 hours after injection (6.26% ± 0.47% injected dose [ID]/g), whereas tumor to muscle and tumor to blood ratios peaked at 48 hours. The 24-hour tumor uptake decreased to 3.43% ± 0.85% ID/g by blocking with unlabeled ATPS mAb. After 4 weeks of treatment, mice receiving 131I-ATPS mAb had significantly smaller tumors (679.4 ± 232.3 mm3) compared with control (1687.6 ± 420.4 mm3, P = .0431) and IgG-treated mice (2870.2 ± 484.1 mm3, P = .0010). The percentage of TGI of 131I-ATPS mAb was greater than 50% during the entire study period (range: 53.7%-75.9%). CONCLUSION: The specific binding and antitumor effects of radioiodinated ATPS mAb were confirmed in in vitro and in vivo models of stomach cancer.

Enhancing the Therapeutic Efficacy of 2-Deoxyglucose in Breast Cancer Cells Using Cell-cycle Synchronization.

AIM: We assessed the effect of cell-cycle synchronization using the T-type calcium channel inhibitor mibefradil on the anticancer effects of 2-deoxy-D-glucose (2-DG) and glucose metabolism in breast cancer cells. MATERIALS AND METHODS: MDA-MB-231 cells were treated with mibefradil, followed by 2-DG with/without paclitaxel, then cells were assessed for viability. Glucose metabolism was evaluated by 3H-2-DG uptake, lactate concentration, and membrane glucose transporter 1 expression after mibefradil treatment. RESULTS: Viability was significantly lower in cells receiving the combination therapy of mibefradil and 2-DG relative to 2-DG treatment alone; addition of paclitaxel to the combination therapy further reduced the viability of breast cancer cells. Withdrawal of mibefradil resulted in a significant increase in cellular 3H-2-DG uptake uptake, a slight accumulation of lactate, and increased membrane glucose transporter 1 expression. CONCLUSION: Mibefradil-induced cell-cycle synchronization enhanced the anticancer activity of 2-DG in breast cancer cells due to an increase in cellular glucose metabolism.