title: Development of targeted near-infrared imaging agents for prostate cancer.
abstract: Prostate cancer is the most common noncutaneous malignancy affecting men in North America. Radical prostatectomy remains a definitive treatment for prostate cancer. However, prostate surgeries are still performed "blindly" with the extent of tumor infiltration past the margins of the surgery only being determined postoperatively. An imaging modality that can be used during surgery is needed to help define the tumor margins. With its abundant expression in prostate cancer, prostate-specific membrane antigen (PSMA) is an ideal target for detection of prostate cancer. The purpose of this study was to develop PSMA-targeted near-infrared (NIR) optical imaging probes for intraoperative visualization of prostate cancer. We synthesized a high-affinity PSMA ligand (PSMA-1) with low molecular weight and further labeled it with commercially available NIR dyes IRDy800 and Cy5.5. PSMA-1 and PSMA-1-NIR conjugates had binding affinities better than the parent ligand Cys-CO-Glu. Selective binding was measured for each of the probes in both in vitro and in vivo studies using competitive binding and uptake studies. Interestingly, the results indicated that the pharmacokinetics of the probes was dependent of the fluorophore conjugated to the PSMA-1 ligand and varied widely. These data suggest that PSMA-targeted probes have the potential to be further developed as contrast agents for clinical intraoperative fluorescence-guided surgery.
authors.affiliation: Department of Radiology and NFCR Center for Molecular Imaging, Case Western Reserve University, Cleveland, Ohio.
authors.forename: Xinning
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Nuclear Medicine, Cleveland Clinic, Cleveland, Ohio.
authors.forename: Steve S
authors.initials: SS
authors.lastname: Huang
authors.affiliation: Department of Cancer Biology, Cleveland Clinic, Cleveland, Ohio.
authors.forename: Warren D W
authors.initials: WD
authors.lastname: Heston
authors.affiliation: Departments of Medicine, Pharmacology and Oncology, MetroHealth Campus, Case Western Reserve University School of Medicine, Cleveland, Ohio.
authors.forename: Hong
authors.initials: H
authors.lastname: Guo
authors.affiliation: Departments of Medicine, Pharmacology and Oncology, MetroHealth Campus, Case Western Reserve University School of Medicine, Cleveland, Ohio.
authors.forename: Bing-Cheng
authors.initials: BC
authors.lastname: Wang
authors.affiliation: Department of Radiology and NFCR Center for Molecular Imaging, Case Western Reserve University, Cleveland, Ohio. jxb206@case.edu.
authors.forename: James P
authors.initials: JP
authors.lastname: Basilion
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000737:chemistry; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000737:chemistry; D005456:Fluorescent Dyes / Q000737:chemistry*; D043425:Glutamate Carboxypeptidase II / Q000737:chemistry; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000473:pathology; D019265:Spectroscopy, Near-Infrared / Q000379:methods*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000954:Antigens, Surface; D003287:Contrast Media; D005456:Fluorescent Dyes; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II