Abstract |
The potent and selective prostanoid EP4 receptor antagonist CJ-042794 was radiolabeled with 18F, and evaluated for imaging EP4 receptor expression in cancer with positron emission tomography (PET). The fluorination precursor, arylboronic acid pinacol ester 4, was prepared in 4 steps with 42% overall yield. 18F-CJ-042794 was synthesized via a copper-mediated 18F-fluorination reaction followed by base hydrolysis, and was obtained in 1.5±1.1% (n=2) decay-corrected radiochemical yield. PET/CT imaging and biodistribution studies in mice showed that 18F-CJ-042794 was excreted through both renal and hepatobiliary pathways with significant retention in blood. The EP4-receptor-expressing LNCaP prostate cancer xenografts were clearly visualized in PET images with 1.12±0.08%ID/g (n=5) uptake value and moderate tumour-to-muscle contrast ratio (2.73±0.22) at 1h post-injection. However, the tumour uptake was nonspecific as it could not be blocked by co-injection of cold standard, precluding the application of 18F-CJ-042794 for PET imaging of EP4 receptor expression in cancer.
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Authors | Zhengxing Zhang, Joseph Lau, Hsiou-Ting Kuo, Chengcheng Zhang, Nadine Colpo, François Bénard, Kuo-Shyan Lin |
Journal | Bioorganic & medicinal chemistry letters
(Bioorg Med Chem Lett)
Vol. 27
Issue 10
Pg. 2094-2098
(05 15 2017)
ISSN: 1464-3405 [Electronic] England |
PMID | 28377057
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2017 Elsevier Ltd. All rights reserved. |
Chemical References |
- (S)-4-(1-(5-chloro-2-(4-fluorophenyoxy) benzamido)ethyl) benzoic acid
- Benzamides
- Fluorine Radioisotopes
- Radiopharmaceuticals
- Receptors, Prostaglandin E, EP4 Subtype
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Topics |
- Animals
- Benzamides
(chemical synthesis, chemistry, pharmacokinetics)
- Cell Line, Tumor
- Fluorine Radioisotopes
(chemistry)
- Humans
- Male
- Mice
- Positron Emission Tomography Computed Tomography
- Prostatic Neoplasms
(diagnostic imaging)
- Radiopharmaceuticals
(chemical synthesis, chemistry, pharmacokinetics)
- Receptors, Prostaglandin E, EP4 Subtype
(chemistry, metabolism)
- Tissue Distribution
- Transplantation, Heterologous
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