Synthesis and Bio-Evaluation of New (18) F-Labeled Pyridaben Analogs with Improved Stability for Myocardial Perfusion Imaging in Mice.

Abstract

To improve the stability of (18) F-labeled pyridaben analogs for myocardial perfusion imaging, three new analogs of pyridaben ([(18) F]FPTP2, [(18) F]FPTP-P2, and [(18) F]FPTP-P3) were synthesized with 'side chain' modifications. The radiolabeled tracers and corresponding non-radioactive compounds were obtained by substituting tosyl group with (18/19) F. The effect of structure modification on myocardial targeting and physicochemical properties of new tracers were evaluated in vitro and in vivo. The total radiosynthesis time of these tracers was approximately 70-90 min with high decay-corrected radiochemical yields (36-65%) and good radiochemical purity (> 98%). These lipophilic tracers exhibited obvious improved stability in water. Studies of their biodistribution in normal Kunming mice demonstrated that [(18) F]FPTP2 exhibited very high initial heart uptake (39.70 ± 2.81 %ID/g at 2 min after injection) and low background in the liver, blood, and soft tissues. The heart-to-liver, heart-to-lung, and heart-to-blood ratios were 3.59, 19.34, and 67.34 at 15 min postinjection, respectively. Favorable myocardial targeting property and remarkable improvement of stability of [(18) F]FPTP2 suggest that the substitution of the phenyl 'sidechain' with other non-phenyl rings has no effect on the myocardial targeting property of (18) F-labeled pyridaben analogs.