title: Radiohalogenated prostate-specific membrane antigen (PSMA)-based ureas as imaging agents for prostate cancer.
abstract: To extend our development of new imaging agents targeting the prostate-specific membrane antigen (PSMA), we have used the versatile intermediate 2-[3-(5-amino-1-carboxy-pentyl)-ureido]-pentanedioic acid (Lys-C(O)-Glu), which allows ready incorporation of radiohalogens for single photon emission computed tomography (SPECT) and positron emission tomography (PET). We prepared 2-[3-[1-carboxy-5-(4-[(125)I]iodo-benzoylamino)-pentyl]-ureido]-pentanedioic acid ([(125)I]3), 2-[3-[1-carboxy-5-(4-[(18)F]fluoro-benzoylamino)-pentyl]-ureido]-pentanedioic acid ([(18)F]6), and 2-(3-[1-carboxy-5-[(5-[(125)I]iodo-pyridine-3-carbonyl)-amino]-pentyl]-ureido)-pentanedioic acid ([(125)I]8) in 65-80% (nondecay-corrected), 30-35% (decay corrected), and 59-75% (nondecay-corrected) radiochemical yields. Compound [(125)I]3 demonstrated 8.8 +/- 4.7% injected dose per gram (%ID/g) within PSMA(+) PC-3 PIP tumor at 30 min postinjection, which persisted, with clear delineation of the tumor by SPECT. Similar tumor uptake values at early time points were demonstrated for [(18)F]6 (using PET) and [(125)I]8. Because of the many radiohalogenated moieties that can be attached via the epsilon amino group, the intermediate Lys-C(O)-Glu is an attractive template upon which to develop new imaging agents for prostate cancer.
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins Medical Institutions, Baltimore, Maryland 21231, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Foss
authors.forename: Youngjoo
authors.initials: Y
authors.lastname: Byun
authors.forename: Sridhar
authors.initials: S
authors.lastname: Nimmagadda
authors.forename: Mrudula
authors.initials: M
authors.lastname: Pullambhatla
authors.forename: James J
authors.initials: JJ
authors.lastname: Fox
authors.forename: Mark
authors.initials: M
authors.lastname: Castanares
authors.forename: Shawn E
authors.initials: SE
authors.lastname: Lupold
authors.forename: John W
authors.initials: JW
authors.lastname: Babich
authors.forename: Ronnie C
authors.initials: RC
authors.lastname: Mease
authors.forename: Martin G
authors.initials: MG
authors.lastname: Pomper
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry; D000818:Animals; D000954:Antigens, Surface / Q000096:biosynthesis* / Q000737:chemistry; D001665:Binding Sites; D002626:Chemistry, Pharmaceutical / Q000379:methods; D019295:Computational Biology / Q000379:methods; D003952:Diagnostic Imaging / Q000295:instrumentation / Q000379:methods; D015195:Drug Design; D043425:Glutamate Carboxypeptidase II / Q000096:biosynthesis* / Q000737:chemistry; D006801:Humans; D008297:Male; D008958:Models, Molecular; D008968:Molecular Conformation; D011471:Prostatic Neoplasms / Q000378:metabolism*; D011485:Protein Binding; D019275:Radiopharmaceuticals / Q000494:pharmacology
chemical_list: D000954:Antigens, Surface; D019275:Radiopharmaceuticals; D000255:Adenosine Triphosphate; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II