title: 68Ga-labeled inhibitors of prostate-specific membrane antigen (PSMA) for imaging prostate cancer.
abstract: Gallium-68 is a generator-produced radionuclide for positron emission tomography (PET) that is being increasingly used for radiolabeling of tumor-targeting peptides. Compounds [(68)Ga]3 and [(68)Ga]6 are high-affinity urea-based inhibitors of the prostate-specific membrane antigen (PSMA) that were synthesized in decay-uncorrected yields ranging from 60% to 70% and radiochemical purities of more than 99%. Compound [(68)Ga]3 demonstrated 3.78 +/- 0.90% injected dose per gram of tissue (%ID/g) within PSMA+ PIP tumor at 30 min postinjection, while [(68)Ga]6 showed a 2 h PSMA+ PIP tumor uptake value of 3.29 +/- 0.77 %ID/g. Target (PSMA+ PIP) to nontarget (PSMA- flu) ratios were 4.6 and 18.3, respectively, at those time points. Both compounds delineated tumor clearly by small animal PET. The urea series of imaging agents for PSMA can be radiolabeled with (68)Ga, a cyclotron-free isotope useful for clinical PET studies, with maintenance of target specificity.
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins Medical Institutions, 1550 Orleans Street, Baltimore, Maryland 21231, USA.
authors.forename: Sangeeta Ray
authors.initials: SR
authors.lastname: Banerjee
authors.forename: Mrudula
authors.initials: M
authors.lastname: Pullambhatla
authors.forename: Youngjoo
authors.initials: Y
authors.lastname: Byun
authors.forename: Sridhar
authors.initials: S
authors.lastname: Nimmagadda
authors.forename: Gilbert
authors.initials: G
authors.lastname: Green
authors.forename: James J
authors.initials: JJ
authors.lastname: Fox
authors.forename: Andrew
authors.initials: A
authors.lastname: Horti
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; D005710:Gallium Radioisotopes; D006801:Humans; D007553:Isotope Labeling; D008297:Male; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D049268:Positron-Emission Tomography; D017430:Prostate-Specific Antigen / Q000037:antagonists & inhibitors*; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D014018:Tissue Distribution; D014183:Transplantation, Heterologous
chemical_list: C551626:2-(3-(1-carboxy-5-(7-(5-carboxy-5-(3-phenyl-2-(3-phenyl-2-(2-(4,7,10-triscarboxymethyl-1,4,7,10-tetraazacyclododec-1-yl)acetylamino)propionylamino)propionylamino)pentylcarbamoyl)heptanoylamino)pentyl)ureido)pentanedioic acid gallium(III); C551625:2-(3-(5-(7-(1-benzyloxycarbonyl-5-(2-(4,7,10-triscarboxymethyl-1,4,7,10-tetraazacyclododec-1-yl)acetylamino)pentylcarbamoyl)heptanoylamino)-1-carboxypentyl)ureido)pentanedioic acid gallium(III); D005710:Gallium Radioisotopes; D009942:Organometallic Compounds; D019275:Radiopharmaceuticals; D017430:Prostate-Specific Antigen