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7121396 
Journal Article 
PET radiotracer [F-18]-P6 selectively targeting COX-1 as a novel biomarker in ovarian cancer: Preliminary investigation 
Perrone, MG; Tantawy, MN; Manning, HC; Marnett, LJ; Scilimati, A; Malerba, P; Uddin, MdJ; Vitale, P; Panella, A; Crews, BC; Daniel, CK; Ghebreselasie, K; Nickels, M; , 
2014 
Yes 
European Journal of Medicinal Chemistry
ISSN: 0223-5234
EISSN: 1768-3254 
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER 
PARIS 
562-568 
24832612 
WOS:000337985400048 
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 ([F-18/19]-P6) is the most promising derivative [IC50 = 2.0 mu M (purified oCOX-1) and 1.37 mu M (hOVCAR-3 cell COX-1)]. Its tosylate precursor was also prepared and, a method for radio[F-18]chemistry was developed and optimized. The radiochemistry was carried out using a carrier-free (KF)-F-18/Kryptofix 2.2.2 complex, that afforded [F-18]-P6 in good radiochemical yield (18%) and high purity (>95%). In vivo PET/CT imaging data showed that the radiotracer [F-18]-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 [F-18]-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. (C) 2014 Elsevier Masson SAS. All rights reserved.