Synthesis and bioevaluation of 4-chloro-2-tert-butyl-5-[2-[[1-[2-[18F]fluroethyl]-1H-1,2,3-triazol-4-yl]methyl]phenylmethoxy]-3(2H)-pyridazinone as potential myocardial perfusion imaging agent with PET

This study reports the synthesis and characterization of 4-chloro-2-tert-butyl-5-[2-[[1-[2-[F-18]fluroethyl]-1H-1,2,3-triazol-4-yl]methyl]phenylmethoxy]-3(2H)-pyridazinone ([F-18]Fmp2) for myocardial perfusion imaging (MPI). The tosylate precursor and non-radioactive compound [F-19]Fmp2 were synthesized and characterized by infrared, H-1-NMR, C-13-NMR, and mass spectra (MS). The radiotracer [F-18]Fmp2 was obtained by one-step nucleophilic substitution of tosyl with F-18, and evaluated as an MPI agent in vitro and in vivo. Starting from [F-18]KF/K-222 solution, the typical decay-corrected radiochemical yield (RCY) was 38 +/- 8.8% with high radiochemical purity (>98%). The specific activity was calculated as 10GBq/mu mol at the end of synthesis determined by HPLC analysis. In the mice biodistribution, [F-18]Fmp2 showed very high initial heart uptake (53.35 +/- 5.47 %ID/g at 2min after injection) and remarkable retention. The heart/liver, heart/lung, and heart/blood ratios were 7.98, 8.20, and 53.13, respectively at 2min post-injection. In the Positron Emission Tomography (PET) imaging study of Chinese mini-swine, the standardized uptake value of the liver decreased modestly during the 2h post-injection, while the heart uptake and heart/liver ratios continued to increase with time. [F-18]Fmp2 exhibited good stability, high heart uptake and low lung uptake in mice and Chinese mini-swine. It may be worthy of further modification to improve liver clearance for MPI in the future.