H. Manning
Faculty Member
Last active: 3/22/2018

PET radiotracer [¹⁸F]-P6 selectively targeting COX-1 as a novel biomarker in ovarian cancer: preliminary investigation.

Perrone MG, Malerba P, Uddin J, Vitale P, Panella A, Crews BC, Daniel CK, Ghebreselasie K, Nickels M, Tantawy MN, Manning HC, Marnett LJ, Scilimati A
Eur J Med Chem. 2014 80: 562-568

PMID: 24832612 · PMCID: PMC4401082 · DOI:10.1016/j.ejmech.2014.04.074

Cyclooxygenase-1 (COX-1), but not COX-2, is expressed at high levels in the early stages of human epithelial ovarian cancer where it seems to play a key role in cancer onset and progression. As a consequence, COX-1 is an ideal biomarker for early ovarian cancer detection. A series of novel fluorinated COX-1-targeted imaging agents derived from P6 was developed by using a highly selective COX-1 inhibitor as a lead compound. Among these new compounds, designed by structural modification of P6, 3-(5-chlorofuran-2-yl)-5-(fluoromethyl)-4-phenylisoxazole ([(18/19)F]-P6) is the most promising derivative [IC50 = 2.0 μM (purified oCOX-1) and 1.37 μM (hOVCAR-3 cell COX-1)]. Its tosylate precursor was also prepared and, a method for radio[(18)F]chemistry was developed and optimized. The radiochemistry was carried out using a carrier-free K(18)F/Kryptofix 2.2.2 complex, that afforded [(18)F]-P6 in good radiochemical yield (18%) and high purity (>95%). In vivo PET/CT imaging data showed that the radiotracer [(18)F]-P6 was selectively taken up by COX-1-expressing ovarian carcinoma (OVCAR 3) tumor xenografts as compared with the normal leg muscle. Our results suggest that [(18)F]-P6 might be an useful radiotracer in preclinical and clinical settings for in vivo PET-CT imaging of tissues that express elevated levels of COX-1.

Copyright © 2014 Elsevier Masson SAS. All rights reserved.

MeSH Terms (17)

Animals Biomarkers, Tumor Cell Line, Tumor Cell Transformation, Neoplastic Cyclooxygenase 1 Cyclooxygenase Inhibitors Female Fluorine Radioisotopes Furans Humans Isoxazoles Mice Ovarian Neoplasms Positron-Emission Tomography Radioactive Tracers Radiochemistry Tomography, X-Ray Computed

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