title: ⁶⁴Cu-labeled inhibitors of prostate-specific membrane antigen for PET imaging of prostate cancer.
abstract: Prostate-specific membrane antigen (PSMA) is a well-recognized target for identification and therapy of a variety of cancers. Here we report five (64)Cu-labeled inhibitors of PSMA, [(64)Cu]3-7, which are based on the lysine-glutamate urea scaffold and utilize a variety of macrocyclic chelators, namely NOTA(3), PCTA(4), Oxo-DO3A(5), CB-TE2A(6), and DOTA(7), in an effort to determine which provides the most suitable pharmacokinetics for in vivo PET imaging. [(64)Cu]3-7 were prepared in high radiochemical yield (60-90%) and purity (>95%). Positron emission tomography (PET) imaging studies of [(64)Cu]3-7 revealed specific accumulation in PSMA-expressing xenografts (PSMA+ PC3 PIP) relative to isogenic control tumor (PSMA- PC3 flu) and background tissue. The favorable kinetics and high image contrast provided by CB-TE2A chelated [(64)Cu]6 suggest it as the most promising among the candidates tested. That could be due to the higher stability of [(64)Cu]CB-TE2A as compared with [(64)Cu]NOTA, [(64)Cu]PCTA, [(64)Cu]Oxo-DO3A, and [(64)Cu]DOTA chelates in vivo.
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins Medical Institutions , 1550 Orleans Street, Baltimore, Maryland 21287, United States.
authors.forename: Sangeeta Ray
authors.initials: SR
authors.lastname: Banerjee
authors.forename: Mrudula
authors.initials: M
authors.lastname: Pullambhatla
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Foss
authors.forename: Sridhar
authors.initials: S
authors.lastname: Nimmagadda
authors.forename: Riccardo
authors.initials: R
authors.lastname: Ferdani
authors.forename: Carolyn J
authors.initials: CJ
authors.lastname: Anderson
authors.forename: Ronnie C
authors.initials: RC
authors.lastname: Mease
authors.forename: Martin G
authors.initials: MG
authors.lastname: Pomper
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002614:Chelating Agents / Q000138:chemical synthesis / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D003300:Copper / Q000737:chemistry; D003301:Copper Radioisotopes; D043425:Glutamate Carboxypeptidase II / Q000378:metabolism; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007202:Indicators and Reagents; D007553:Isotope Labeling / Q000379:methods; D008297:Male; D051379:Mice; D009368:Neoplasm Transplantation; D049268:Positron-Emission Tomography; D017430:Prostate-Specific Antigen / Q000037:antagonists & inhibitors*; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D051381:Rats; D013056:Spectrophotometry, Ultraviolet; D014018:Tissue Distribution; D014057:Tomography, X-Ray Computed; D014915:Whole-Body Counting
chemical_list: D002614:Chelating Agents; D003301:Copper Radioisotopes; D007202:Indicators and Reagents; D019275:Radiopharmaceuticals; D003300:Copper; D043425:Glutamate Carboxypeptidase II; D017430:Prostate-Specific Antigen