Synthesis and Evaluation of (18)F-labeled Pyridaben Analogues for Myocardial Perfusion Imaging in Mice, Rats and Chinese mini-swine.

Tiantian Mou,Zuoquan Zhao,Qian Wang,Jie Lu,Xianzhong Zhang,Wei Fang,Linyi You,Cheng Peng,Yesen Li

doi:10.1038/srep33450

Abstract

This study reports three novel 18F-labeled pyridaben analogues for potential myocardial perfusion imaging (MPI). Three precursors and the corresponding nonradioactive compounds were synthesized and characterized. The radiolabeled tracers were obtained by substituting tosyl with 18F. The total radiosynthesis time of these tracers was 70–90 min. Typical decay-corrected radiochemical yields were 47–58%, with high radiochemical purities (>98%). Tracers were evaluated as MPI agents in vitro, ex vivo and in vivo. In the mouse biodistribution study, all three radiotracers showed high initial heart uptake (34–54% ID/g at 2 min after injection) and fast liver clearance. In the microPET imaging study, [18F]Fmpp2 produced heart images with good quality in both mice and rats. In the whole-body PET/CT images of mini-swine, [18F]Fmpp2 showed excellent initial heart standardized uptake value (SUV) (7.12 at 5 min p.i.) and good retention (5.75 at 120 min p.i.). The heart/liver SUV ratios were 4.12, 5.42 and 5.99 at 30, 60 and 120 min after injection, respectively. The favorable biological properties of [18F]Fmpp2 suggest that it is worth further investigation as a potential MPI agent.

Highlights

This study reports three novel 18F-labeled pyridaben analogues for potential myocardial perfusion imaging (MPI)
Our group reported a series of pyridaben analogues as potential MPI agents22–25. [18F]FP1OP exhibits the most promising biological properties with high initial heart uptake and good target-to-background ratios
Compared with previously reported compounds of [18F]FP1OP23 and [18F]FP2OP24, [18F]Fmpp[2] had better stability in a water solution, which is propitious to the long-distance transport

Summary

Introduction

This study reports three novel 18F-labeled pyridaben analogues for potential myocardial perfusion imaging (MPI). [18F]Fmpp1, [18F]Fmpp[2] and [18F]Fmpp[3] had high initial heart uptake (54.82 ± 5.74, 42.38 ± 4.40 and 34.01 ± 3.54% ID/g at 2 min post-injection (p.i.), respectively) and good target/non-target ratios. All three tracers were washed out quickly from the heart (approximately 82%, 57% and 62% of the radioactivity was cleared from the heart for [18F]Fmpp1, [18F]Fmpp[2] and [18F] Fmpp[3], respectively, at 60 min p.i. compared with that at 2 min p.i.), which affected the heart/liver ratios at subsequent time points.

Results

Conclusion