A low molecular weight PSMA-based fluorescent imaging agent for cancer

Biochem Biophys Res Commun. 2009 Dec 18;390(3):624-9. doi: 10.1016/j.bbrc.2009.10.017. Epub 2009 Oct 8.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antigens, Surface / chemistry
  • Cell Line, Tumor
  • Fluorescent Dyes / chemical synthesis
  • Fluorescent Dyes / chemistry
  • Fluorescent Dyes / pharmacokinetics*
  • Glutamate Carboxypeptidase II / chemistry
  • Glutamate Carboxypeptidase II / pharmacokinetics*
  • Glutamates / chemical synthesis
  • Glutamates / chemistry
  • Glutamates / pharmacokinetics*
  • Humans
  • Indoles / chemistry
  • Male
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Molecular Weight
  • Prostatic Neoplasms / metabolism*
  • Urea / analogs & derivatives*
  • Urea / chemical synthesis
  • Urea / chemistry
  • Urea / pharmacokinetics

Substances

  • Antigens, Surface
  • Fluorescent Dyes
  • Glutamates
  • IRDye800
  • Indoles
  • YC-27 compound
  • Urea
  • FOLH1 protein, human
  • Glutamate Carboxypeptidase II