PET radiotracer [¹8F]-P6 selectively targeting COX-1 as a novel biomarker in ovarian cancer: preliminary investigation.
Eur J Med Chem
; 80: 562-568, 2014 Jun 10.
Article
em En
| MEDLINE
| ID: mdl-24832612
ABSTRACT
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.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Ovarianas
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Radioisótopos de Flúor
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Biomarcadores Tumorais
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Tomografia por Emissão de Pósitrons
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Ciclo-Oxigenase 1
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Furanos
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Isoxazóis
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Eur J Med Chem
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Itália