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Synthesis of (4-$[^{18}F]$Fluorophenyl)triphenylphosphonium as a Mitochondrial Voltage Sensor for PET  

Kim, Dong-Yeon (Department of Nuclear Medicine, Chonnam National University Medical School)
Yu, Kook-Hyun (Department of Chemistry, Dongguk University)
Bom, Hee-Seung (Department of Nuclear Medicine, Chonnam National University Medical School)
Min, Jung-Joon (Department of Nuclear Medicine, Chonnam National University Medical School)
Publication Information
Nuclear Medicine and Molecular Imaging / v.41, no.6, 2007 , pp. 561-565 More about this Journal
Abstract
Purpose: Lipophilic cations including tetraphenylphosphonium (TPP) salts penetrate the hydrophobic barriers of the plasma and mitochondrial membranes, resulting in accumulation in mitochondria in response to the negative inner transmembrane potentials. The development of radiolabeled phosphonium cations as a noninvasive imaging agent may serve as a new molecular "voltage sensor" probe to investigate the role of mitochondria in the pathophysiology and diagnosis of cancer. Materials and Methods: We have synthesized a reference compound (4-fluorophenyl)triphenylphosphonium (TPP) and a labeled compound $[^{18}F]$TPP via two step nucleophilic substitution of no-carrier-added $[^{18}F]$fluoride with the precursor, 4-iodophenyltrimethylammonium iodide, in the presence of Kryptofix-2.2.2 and $K_2CO_3$. Result: The reference compound (4-fluorophenyl)triphenylphosphonium (TPP) was synthesized in 60% yield. The radiolabeled compound $[^{18}F]$TPP was synthesized in $10\sim15%$ yield. The radiochemical purity of the $[^{18}F]$TPP was $95.57{\pm}0.51%$ (n=11). Conclusion: $[^{18}F]$TPP was successfully synthesized that might have a potential to be utilized as a novel myocardial or cancer imaging agent for PET. However, it is required to improve the radiochemical yield to apply $[^{18}F]$TPP in preclinical or clinical researches.
Keywords
phosphonium salts; tetraphenylphosphonium; mitochondrial membrane potential; PET; myocardial imaging; cancer imaging;
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