Nucl Med Mol Imaging.  2007 Dec;41(6):561-565.

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

• Kim DY
• Yu KH
• Bom HS
• Min JJ

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 [18F]TPP via two step nucleophilic substitution of no-carrier-added [18F]fluoride with the precursor, 4-iodophenyltrimethylammonium iodide, in the presence of Kryptofix-2.2.2 and K2CO3. RESULT: The reference compound (4-fluorophenyl)triphenylphosphonium (TPP) was synthesized in 60% yield. The radiolabeled compound [18F]TPP was synthesized in 10~15% yield. The radiochemical purity of the [18F]TPP was 95.57+/-0.51% (n=11).
CONCLUSION
[18F]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 [18F]TPP in preclinical or clinical researches.

Keyword

phosphonium salts; tetraphenylphosphonium; mitochondrial membrane potential; PET; myocardial imaging; cancer imaging

MeSH Terms

Cations
Diagnosis
Membrane Potential, Mitochondrial
Membrane Potentials
Mitochondria
Mitochondrial Membranes
Plasma
Salts
Cations
Salts