Journal
MOLECULAR PHARMACEUTICS
Volume 11, Issue 11, Pages 3823-3831Publisher
AMER CHEMICAL SOC
DOI: 10.1021/mp500216g
Keywords
F-18-labeled phosphonium cation; one-pot radiosynthesis; positron emission tomography; biodistribution; myocardial perfusion imaging agent
Funding
- National Key Basic Research Program of China [2014CB744503]
- National Natural Science Foundation of China [21271030, 20871020, 81301251]
- Department of Nuclear Medicine of Peking Union Medical College Hospital
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Lipophilic cations such as phosphonium salts can accumulate in mitochondria of heart in response to the negative inner-transmembrane potentials. Two phosphonium salts [F-18]FMBTP and [F-18]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 [F-18]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 [F-18] labeled compounds were obtained in high radiolabeling yield (similar to 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 [F-18]FMBTP and [F-18]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.
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