Synthesis and preclinical evaluation of an 18F-labeled 1,5-diarylpyrrole derivative for imaging of COX-2 expression.

Abstract

Cyclooxygenase-2 (COX-2) plays vital roles in promoting angiogenesis, tissue invasion, and resistance to apoptosis, so it has become an attractive biomarker for imaging and therapy of cancer. Numerous radio-tracers for detection of COX-2 in vivo have been reported, but no one has been successfully applied in clinic. In this study, the radiosynthesis and evaluation of [¹⁸F]6, containing a 1,5-diarylpyrrole structure, as a radiotracer for imaging of COX-2 is described. [¹⁸F]6 was prepared within 90 min synthesis time with radiochemical yields (RCYs) of 2-6% (n = 7, decay corrected) from [¹⁸F]fluoride by a one-step ¹⁸F-trifluoromethylation reaction. After purification by high performance liquid chromatography (HPLC), its radiochemical purity (RCP) was higher than 98%, and the molar activity was 156-210 MBq/mmol. The stability of [¹⁸F]6 was determined by incubation in saline and fetal bovine serum (FBS) in vitro, showing excellent stability in 4 h. The specific binding of [¹⁸F]6 was evaluated using MCF-7 cells (COX-2 positive cells) in vitro, where the radiotracer uptake was blocked in the presence of Celecoxib (a commonly used COX-2 inhibitor). However, no tumor accumulation of [¹⁸F]6 could be observed by micro-PET/CT studies on MCF-7 tumor-bearing mice in vivo. This may be due to the insufficient molar activity of [¹⁸F]6, or inadequate expression of COX-2 in MCF-7. In conclusion, optimizations of radiosynthesis and evaluations of specific binding in suitable model are further still needed to verify the potential of [¹⁸F]6 as a COX-2 imaging agent.