title: A low molecular weight PSMA-based fluorescent imaging agent for cancer.
abstract: We synthesized YC-27 3 to provide a fluorescent imaging agent for the prostate-specific membrane antigen (PSMA), a marker for hormone-independent prostate cancer and tumor neovasculature, with suitable pharmacokinetics for use in vivo. Immediate precursor trifluoroacetate salt of 2-(3-{5-[7-(5-amino-1-carboxy-pentylcarbamoyl)-heptanoylamino]-1-carboxy-pentyl}-ureido)-pentanedioic acid 2 was conjugated with a commercially available near-infrared light-emitting dye (IRDye 800CW) to provide 3 in 72% yield. YC-27 3 demonstrated a PSMA inhibitory activity of 0.37nM and was capable of generating target-to-nontarget ratios of at least 10 in PSMA-expressing PC3-PIP vs. PSMA-negative PC3-flu tumors in vivo. YC-27 3 may be useful for study of PSMA-expressing tissue in preclinical models or for intraoperative guidance.
authors.affiliation: Russell H Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, 1550 Orleans Street, Baltimore, MD 21231, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.forename: Surajit
authors.initials: S
authors.lastname: Dhara
authors.forename: Sangeeta Ray
authors.initials: SR
authors.lastname: Banerjee
authors.forename: Youngjoo
authors.initials: Y
authors.lastname: Byun
authors.forename: Mrudula
authors.initials: M
authors.lastname: Pullambhatla
authors.forename: Ronnie C
authors.initials: RC
authors.lastname: Mease
authors.forename: Martin G
authors.initials: MG
authors.lastname: Pomper
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000737:chemistry; D045744:Cell Line, Tumor; D005456:Fluorescent Dyes / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics*; D043425:Glutamate Carboxypeptidase II / Q000737:chemistry / Q000493:pharmacokinetics*; D005971:Glutamates / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics*; D006801:Humans; D007211:Indoles / Q000737:chemistry; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008970:Molecular Weight; D011471:Prostatic Neoplasms / Q000378:metabolism*; D014508:Urea / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D000954:Antigens, Surface; D005456:Fluorescent Dyes; D005971:Glutamates; C427728:IRDye800; D007211:Indoles; C545898:YC-27 compound; D014508:Urea; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II