Repurposing 11C-PS13 for PET Imaging of Cyclooxygenase-1 in Ovarian Cancer Xenograft Mouse Models

Abstract

Cyclooxygenase-1 (COX-1), a biomarker for neuroinflammation, is implicated in the progression and prognosis of ovarian cancer (OvCa). This study considered the repurposing of 11C-labeled 1,5- bis(4-methoxyphenyl)-3-(2,2,2-trifluoroethoxy)-1H-1,2,4-triazole (11CPS13), a COX-1 PET neuroimaging radiopharmaceutical, in OvCa xenograft mouse models. Methods: 11C-PS13 was evaluated in ICRscid mice with subcutaneous or intraperitoneal human OVCAR-3 OvCa xenografts by dynamic PET/MRI, ex vivo biodistribution, and radiometabolite analysis of plasma and tumor. Results: OVCAR-3 xenografts were well visualized with 11C-PS13 in xenograft mouse models. Time-activity curves revealed a steady accumulation of tumor radioactivity that plateaued from 40 to 60 min and was significantly reduced by pretreatment with ketoprofen (3.56 ± 0.81 and 1.30 ± 0.18 percentage injected dose/g without and with pretreatment, respectively, P 5 0.01). Radiometabolite analysis showed that intact 11C-PS13 accounted for more than 80% of radioactivity in the tumor, with less than 20% in plasma, at 40 min after injection. Conclusion: 11C-PS13 shows promise for PET imaging of COX-1 in OvCa, and rapid translation for clinical cancer research should be considered.