A PSMA-targeted theranostic agent for photodynamic therapy

Ying Chen, Samit Chatterjee, Ala Lisok, Il Minn, Mrudula Pullambhatla, Bryan Wharram, Yuchuan Wang, Jiefu Jin, Zaver M Bhujwalla, Sridhar Nimmagadda, Ronnie Mease, Martin Gilbert Pomper

Research output: Contribution to journalArticle

Abstract

Prostate-specific membrane antigen (PSMA) is over-expressed in the epithelium of prostate cancer and in the neovasculature of many non-prostate solid tumors. PSMA has been increasingly used as a target for cancer imaging and therapy. Here we describe a low-molecular-weight theranostic photosensitizer, YC-9, for PSMA-targeted optical imaging and photodynamic therapy (PDT). YC-9 was synthesized by conjugating IRDye700DX N-hydroxysuccinimide (NHS) ester with a PSMA targeting Lys-Glu urea through a lysine-suberate linker in suitable yield. Optical imaging in vivo demonstrated PSMA-specific tumor uptake of YC-9 with rapid clearance from non-target tissues. PSMA-specific cell kill was demonstrated with YC-9 in vitro through PDT in PSMA+ PC3-PIP and PSMA PC3-flu cells. In vivo PDT in mice bearing PSMA+ PC3-PIP tumors at 4 h post-injection of YC-9 (A total of four PDT sessions were performed, 48 h apart) resulted in significant tumor growth delay, while tumors in control groups continued to grow. PDT with YC-9 significantly increased the median survival of the PSMA+ PC3-PIP tumor mice (56.5 days) compared to control groups [23.5–30.0 days, including untreated, light alone, YC-9 alone (without light) and non-targeted IRDye700DX PDT treatment groups], without noticeable toxicity at the doses used. This study proves in principle that YC-9 is a promising therapeutic agent for targeted PDT of PSMA-expressing tissues, such as prostate tumors, and may also be useful against non-prostate tumors by virtue of neovascular PSMA expression.

Original languageEnglish (US)
Pages (from-to)111-116
Number of pages6
JournalJournal of Photochemistry and Photobiology B: Biology
Volume167
DOIs
StatePublished - Feb 1 2017

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Keywords

  • Molecular imaging
  • Optical imaging
  • PDT
  • Prostate cancer
  • Prostate-specific membrane antigen

ASJC Scopus subject areas

  • Radiation
  • Radiological and Ultrasound Technology
  • Biophysics
  • Radiology Nuclear Medicine and imaging

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