Radiosynthesis& biological evaluation of 11C-HIQPM as a novel PET tracer for apoptosis

604 Objectives: Identification of apoptosis in vivo might be helpful for assessing tumor response to cancer therapy or other clinical practices. Targeting effector caspases is an efficient approach for apoptosis imaging. N-(4-hydroxybenzyl)-N-(2-[11C]methyl-1,3,4-trioxo- 1,2,3,4- tetrahydroisoquinolin-6-yl)succinamide (11C-HIQPM), a derivative of the small molecular caspase 3 inhibitor 1,3,4-trione-isoquinoline, was radio labeled & evaluated as a potential apoptosis radiotracer. Methods: Radiosynthesis of 11C-HIQPM was performed by N-[11C]-methylation of the demethyl-precursor using [11C]-methyl triflate in the presence of NaOH. A quality control procedure for biological application of 11C-HIQPM was established. In vitro, binding assay of 11C-HIQPM with cisplatin-induced apoptosis of Human Lung Adenocarcinoma Cell Line A549 was performed at different times & compared to that of non-treated cells. Ex vivo bio-distribution of 11C-HIQPM in the control group of A549 tumor- bearing nude mice & treated groups of cyclophosphamide-induced apoptosis for 24h &d 48h were analyzed at 30min after injection. Apoptosis imaging in the A549 tumor bearing nude mouse model was acquired before cancer treatment and after treatment to assess therapy- induced apoptosis. Results: 2.2-4.0GBq of 11C-HIQPM was prepared from 15-30 GBq of 11C-CO2. The decay corrected radiochemical yield was 14-18%. The radiochemical purity exceeded 98% and the specific activity was 22.5-32.3 GBq/μmol (n=5) at the end of synthesis. The identity was confirmed via analytical chromatographyby co-injection of 11C-HIQPM and 12C-HIQPM. Cisplatin-treated cells, which were 13.5±1.8 % apoptotic cells, demonstrated higher relative uptake of 11C-HIQPM relative to untreated controls (average twofold increase at 5, 10 and 20 min, p