Highly efficient one-pot labeling of new phosphonium cations with fluorine-18 as potential PET agents for myocardial perfusion imaging.
Lipophilic cations such as phosphonium salts can accumulate in mitochondria of heart in response to the negative inner-transmembrane potentials. Two phosphonium salts [(18)F]FMBTP and [(18)F]mFMBTP were prepared and evaluated as potential myocardial perfusion imaging (MPI) agents in this study. The cations were radiolabeled via a simplified one-pot method starting from [(18)F]fluoride and followed by physicochemical property tests, in vitro cellular uptake assay, ex vivo mouse biodistribution, and in vivo rat microPET imaging. The total radiosynthesis time was less than 60 min including HPLC purification. The [(18)F] labeled compounds were obtained in high radiolabeling yield (∼50%) and good radiochemical purity (>99%). Both compounds were electropositive, and their log P values at pH 7.4 were 1.16 ± 0.003 (n = 3) and 1.05 ± 0.01 (n = 3), respectively. Both [(18)F]FMBTP and [(18)F]mFMBTP had high heart uptake (25.24 ± 2.97% ID/g and 31.02 ± 0.33% ID/g at 5 min postinjection (p.i.)) in mice with good retention (28.99 ± 3.54% ID/g and 26.82 ± 3.46% ID/g at 120 min p.i.). From the PET images in rats, the cations exhibited high myocardium uptake and fast clearance from liver and small intestine to give high-contrast images across all time points. These phosphonium cations were radiosynthesized via a highly efficient one-pot procedure for potential MPI offering high heart accumulation and rapid nontarget clearance.
Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University , 19 Xinjiekou Outer Street, Beijing 100875, China.
Zuoquan
Z
Zhao
Qian
Q
Yu
Tiantian
T
Mou
Chang
C
Liu
Wenjiang
W
Yang
Wei
W
Fang
Cheng
C
Peng
Jie
J
Lu
Yu
Y
Liu
Xianzhong
X
Zhang
D000818:Animals; D002412:Cations; D002851:Chromatography, High Pressure Liquid; D004285:Dogs; D005462:Fluorine Radioisotopes; D006321:Heart / Q000000981:diagnostic imaging; D006863:Hydrogen-Ion Concentration; D007421:Intestine, Small / Q000000981:diagnostic imaging; D008099:Liver / Q000000981:diagnostic imaging; D008297:Male; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D055414:Myocardial Perfusion Imaging / Q000379:methods*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D041681:NIH 3T3 Cells; D010710:Phosphates / Q000737:chemistry*; D049268:Positron-Emission Tomography; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D014057:Tomography, X-Ray Computed
D002412:Cations; D005462:Fluorine Radioisotopes; D010710:Phosphates
18F-labeled phosphonium cation; biodistribution; myocardial perfusion imaging agent; one-pot radiosynthesis; positron emission tomography