A PSMA-targeted theranostic agent for photodynamic therapy.

A PSMA-targeted theranostic agent for photodynamic therapy.

J Photochem Photobiol B. 2016 Dec 18;167:111-116

Authors: Chen Y, Chatterjee S, Lisok A, Minn I, Pullambhatla M, Wharram B, Wang Y, Jin J, Bhujwalla ZM, Nimmagadda S, Mease RC, Pomper MG

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-9in vitro through PDT in PSMA(+) PC3-PIP and PSMA(-) PC3-flu cells. In vivo PDT in mice bearing PSMA(+) PC3-PIP tumors at 4h post-injection of YC-9 (A total of four PDT sessions were performed, 48h 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 (56.5days) compared to control groups [23.5-30.0days, 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.

PMID: 28063300 [PubMed - as supplied by publisher]

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