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Synthesis and Bio‐Evaluation of New 18 F‐Labeled Pyridaben Analogs with Improved Stability for Myocardial Perfusion Imaging in Mice
Author(s) -
Mou Tiantian,
Zhao Zuoquan,
Zhang Pu,
Fang Wei,
Peng Cheng,
Lu Jie,
Wang Qian,
Ma Yunchuan,
Zhang Xianzhong
Publication year - 2015
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12499
Subject(s) - radiosynthesis , biodistribution , chemistry , in vivo , myocardial perfusion imaging , perfusion , tosyl , radiochemistry , in vitro , stereochemistry , biochemistry , medicine , biology , microbiology and biotechnology
To improve the stability of 18 F‐labeled pyridaben analogs for myocardial perfusion imaging, three new analogs of pyridaben ([ 18 F] FPTP 2, [ 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] FPTP 2 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] FPTP 2 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.