title: Synthesis and evaluation of18F-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 with18F, 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-mediated18F-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 that18F-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 of18F-CJ-042794 for PET imaging of EP4 receptor expression in cancer.
authors.affiliation: Department of Molecular Oncology, BC Cancer Agency, Vancouver, BC V5Z 1L3, Canada.
authors.forename: Zhengxing
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Molecular Oncology, BC Cancer Agency, Vancouver, BC V5Z 1L3, Canada.
authors.forename: Joseph
authors.initials: J
authors.lastname: Lau
authors.affiliation: Department of Molecular Oncology, BC Cancer Agency, Vancouver, BC V5Z 1L3, Canada.
authors.forename: Hsiou-Ting
authors.initials: HT
authors.lastname: Kuo
authors.affiliation: Department of Molecular Oncology, BC Cancer Agency, Vancouver, BC V5Z 1L3, Canada.
authors.forename: Chengcheng
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Molecular Oncology, BC Cancer Agency, Vancouver, BC V5Z 1L3, Canada.
authors.forename: Nadine
authors.initials: N
authors.lastname: Colpo
authors.affiliation: Department of Molecular Oncology, BC Cancer Agency, Vancouver, BC V5Z 1L3, Canada; Department of Functional Imaging, BC Cancer Agency, Vancouver, BC V5Z 4E6, Canada; Department of Radiology, University of British Columbia, Vancouver, BC V5Z 4E3, Canada.
authors.forename: François
authors.initials: F
authors.lastname: Bénard
authors.affiliation: Department of Molecular Oncology, BC Cancer Agency, Vancouver, BC V5Z 1L3, Canada; Department of Functional Imaging, BC Cancer Agency, Vancouver, BC V5Z 4E6, Canada; Department of Radiology, University of British Columbia, Vancouver, BC V5Z 4E3, Canada. Electronic address: klin@bccrc.ca.
authors.forename: Kuo-Shyan
authors.initials: KS
authors.lastname: Lin
mesh_terms: D000818:Animals; D001549:Benzamides / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D005462:Fluorine Radioisotopes / Q000737:chemistry; D006801:Humans; D008297:Male; D051379:Mice; D000072078:Positron Emission Tomography Computed Tomography; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D058309:Receptors, Prostaglandin E, EP4 Subtype / Q000737:chemistry / Q000378:metabolism*; D014018:Tissue Distribution; D014183:Transplantation, Heterologous
chemical_list: C523467:(S)-4-(1-(5-chloro-2-(4-fluorophenyoxy) benzamido)ethyl) benzoic acid; D001549:Benzamides; D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals; D058309:Receptors, Prostaglandin E, EP4 Subtype
keywords: Antagonist; CJ-042794; Fluorine-18; Molecular imaging; Positron emission tomography; Prostanoid EP4 receptor