Abstract
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Objectives Prostate-specific membrane antigen (PSMA) is over-expressed in the epithelium of prostate cancer and in non-prostate solid tumor neovasculature, presenting it as a suitable target for cancer imaging and therapy. Here we report a low-molecular-weight (LMW) PSMA-targeted theranostic agent, YC-9, for prostate cancer imaging and photodynamic therapy (PDT).
Methods YC-9 was synthesized through conjugating IRDye700DX NHS ester with a PSMA targeting lysine-glutamate urea through a lysine-suberate linker. Optical imaging was performed in immunocompromised mice bearing PSMA+ PC3 PIP and PSMA- PC3 flu tumors. In vitro PDT effect with YC-9 was investigated using PIP and flu cells. In vivo PDT effect with YC-9 was demonstrated in mice bearing PSMA+ PC3 PIP tumors after two PDT treatments on day 0 and day 1. For each treatment, the mice received an intravenous injection of YC-9 (10 nmol) followed by light irradiation (100 J/cm2) at 4 h post-injection.
Results YC-9 was synthesized in 67% yield. In vivo optical imaging demonstrated PSMA-specific tumor uptake of YC-9 with rapid clearance from non-targeted tissues. PSMA-specific cell kill was achieved with YC-9 in vitro PDT. Tumor growth was significantly inhibited in mice treated with YC-9 PDT compared to other control groups.
Conclusions This study shows that YC-9 is a promising LMW PSMA-targeted theranostic agent for prostate cancer imaging and PDT.
Research Support CA134675