当前位置： SCI文献检索 > NUCLEAR MEDICINE AND BIOLOGY期刊下所有文献 > Synthesis of [18F]-labeled (2-(2-fluoroethoxy)ethyl)tris(4-methoxyphenyl)phosphonium cation as a potential agent for positron emission tomography myocardial imaging.

Synthesis of [18F]-labeled (2-(2-fluoroethoxy)ethyl)tris(4-methoxyphenyl)phosphonium cation as a potential agent for positron emission tomography myocardial imaging.

Abstract：

INTRODUCTION:Established radiotracers for positron emission tomography (PET) myocardial perfusion study are commonly labeled with short-lived radio-isotopes that limit their widespread clinical use. Thus, we synthesized (2-(2-[(18)F]fluoroethoxy)ethyl)tris(4-methoxyphenyl)phosphonium salt ([(18)F]FETMP) as a novel myocardial perfusion agent that penetrates the hydrophobic barriers of the plasma and mitochondrial membranes and accumulate in mitochondria of cardiomyocytes in response to the negative inner-transmembrane potentials. METHODS:The [(18)F]FETMP was synthesized via two-step nucleophilic substitution reactions of no-carrier-added [(18)F]fluoride with the precursor 2,2'-oxybis(ethane-2,1-diyl)bis(4-methylbenzenesulfonate) in the presence of Kryptofix 2.2.2 and K(2)CO(3). The [(18)F]FETMP accumulation was measured in cell culture with rat embryonic cardiomyoblast (H9c2) and mouse normal fibroblast (NIH/3T3) cell lines. The mitochondrial membrane potential-dependent cellular uptake of [(18)F]FETMP was further assessed using the H9c2 cells treated with carbonyl cyanide m-chlorophenylhydrazone (CCCP) which is a protonophore that selectively abolishes the mitochondrial membrane potential. Biodistribution and micro-PET studies were performed in normal BALB/c mice to test and optimize the kinetics for radiolabeled phosphonium cation. RESULTS:The radiolabeled compound was synthesized with 10%-20% yield. The radiochemical purity was >98% by analytical HPLC, and the specific activity was >5.92TBq/μmol. The cellular uptake assay showed preferential uptake of [(18)F]FETMP in cardiomyocytes. The results of biodistribution and micro-PET imaging studies of [(18)F]FETMP in mice and rats showed preferential accumulation in the myocardium. CONCLUSIONS:The results suggest that [(18)F]FETMP would be a promising candidate for myocardial imaging and might be useful for clinical cardiac PET/CT applications.

journal_name

Nucl Med Biol

journal_title

Nuclear medicine and biology

authors

Kim DY,Kim HJ,Yu KH,Min JJ

doi

10.1016/j.nucmedbio.2012.03.008

subject

Has Abstract

pub_date

2012-10-01 00:00:00

pages

1093-8

issue

7

eissn

0969-8051

issn

1872-9614

pii

S0969-8051(12)00082-0

journal_volume

39

pub_type

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