Synthesis and biological evaluation of substrate-based imaging agents for the prostate-specific membrane antigen

Youngjoo Byun, Mrudula Pullambhatla, Haofan Wang, Ronnie Mease, Martin Gilbert Pomper

Research output: Contribution to journalArticle

Abstract

Prostate-specific membrane antigen (PSMA) is an attractive target for the imaging of prostate cancer (PCa) due to the elevated expression on the surface of prostate tumor cells. Most PSMA-targeted low molecular weight imaging agents are inhibitors of PSMA. We have synthesized a series of substrate-based PSMA-targeted imaging agents by mimicking poly-γ-glutamyl folic acid, an endogenous substrate of PSMA. In vitro the γ-linked polyglutamate conjugates proved to be better substrates than the corresponding α-linked glutamates. However, in vivo imaging studies of γ-ray-emitting and γ-linked glutamates did not demonstrate selective uptake in PSMA-positive over PSMA-negative tumors. Subsequent chromatographic studies and in silico molecular dynamics simulations indicated that hydrolysis of the substrates is slow and access to the enzymatic active site is limited. These results inform the design of future substrate-based imaging agents for PSMA.

Original languageEnglish (US)
Pages (from-to)565-573
Number of pages9
JournalMacromolecular Research
Volume21
Issue number5
DOIs
StatePublished - May 2013

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Antigens
Membranes
Imaging techniques
Substrates
Glutamates
Tumors
Polyglutamic Acid
human glutamate carboxypeptidase II
Folic Acid
Molecular dynamics
Hydrolysis
Molecular weight
Cells
Acids
Computer simulation

Keywords

  • molecular imaging
  • prodrug
  • prostate cancer
  • PSMA
  • SPECT

ASJC Scopus subject areas

  • Organic Chemistry
  • Materials Chemistry
  • Polymers and Plastics
  • Chemical Engineering(all)

Cite this

Synthesis and biological evaluation of substrate-based imaging agents for the prostate-specific membrane antigen. / Byun, Youngjoo; Pullambhatla, Mrudula; Wang, Haofan; Mease, Ronnie; Pomper, Martin Gilbert.

In: Macromolecular Research, Vol. 21, No. 5, 05.2013, p. 565-573.

Research output: Contribution to journalArticle

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