A Series of PSMA-Targeted Near-Infrared Fluorescent Imaging Agents

Ying Chen, Il Minn, Steven P. Rowe, Alla Lisok, Samit Chatterjee, Mary Brummet, Sangeeta Ray Banerjee, Ronnie C. Mease, Martin G. Pomper

Research output: Contribution to journalArticlepeer-review

Abstract

We have synthesized a series of 10 new, PSMA-targeted, near-infrared imaging agents intended for use in vivo for fluorescence-guided surgery (FGS). Compounds were synthesized from the commercially available amine-reactive active NHS ester of DyLight800. We altered the linker between the PSMA-targeting urea moiety and the fluorophore with a view to improve the pharmacokinetics. Chemical yields for the conjugates ranged from 51% to 86%. The Ki values ranged from 0.10 to 2.19 nM. Inclusion of an N-bromobenzyl substituent at the ε-amino group of lysine enhanced PSMA+ PIP tumor uptake, as did hydrophilic substituents within the linker. The presence of a polyethylene glycol chain within the linker markedly decreased renal uptake. In particular, DyLight800-10 demonstrated high specific uptake relative to background signal within kidney, confirmed by immunohistochemistry. These compounds may be useful for FGS in prostate, renal or other PSMA-expressing cancers.

Original languageEnglish (US)
Article number405
JournalBiomolecules
Volume12
Issue number3
DOIs
StatePublished - Mar 2022

Keywords

  • DyLight800
  • Fluorescence-guided surgery
  • Molecular imaging
  • NIRF
  • Prostate-specific membrane antigen

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry

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