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Synthesis and evaluation of 18F-labeled CJ-042794 for imaging prostanoid EP4 receptor expression in cancer with positron emission tomography.

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.
AuthorsZhengxing Zhang, Joseph Lau, Hsiou-Ting Kuo, Chengcheng Zhang, Nadine Colpo, François Bénard, Kuo-Shyan Lin
JournalBioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 27 Issue 10 Pg. 2094-2098 (05 15 2017) ISSN: 1464-3405 [Electronic] England
PMID28377057 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 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
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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