Evaluation of Chemotherapy Response in VX2 Rabbit Lung Cancer with 18F-Labeled C2A Domain of Synaptotagmin I

摘要

The C2A domain of synaptotagmin I can target apoptotic cells by binding to exposed anionic phospholipids. The goal of this study was to synthesize and develop ¹⁸F-labeled C2A-gluta-thione-S-transferase (GST) as a molecular imaging probe for the detection of apoptosis and to assess the response of paclitaxel chemotherapy in VX2 rabbit lung cancer.Methods¹⁸F-C2A-GST was prepared by labeling C2A-GST with N-succinimidyl 4-¹⁸F-fluorobenzoate (¹⁸F-SFB). ¹⁸F-C2A-GST was confirmed by high-performance liquid chromatography and sodium dodecyl sulfate polyacrylamide gel electrophoresis. The binding of ¹⁸F-C2A-GST toward apoptosis was validated in vitro using camptothecin-induced Jurkat cells. Biodistribution of ¹⁸F-C2A-GST was determined in mice by a dissection method and small-animal PET. Single-dose paclitaxel was used to induce apoptosis in rabbits bearing VX2 tumors (n = 6), and 2 VX2 rabbits without treatment served as control. ¹⁸F-C2A-GST PET was performed before and at 72 h after therapy, and ¹⁸F-FDG PET/CT was also performed before treatment. To confirm the presence of apoptosis, tumor tissue was analyzed and activated caspase-3 was measured.