A self-triggered radioligand therapy agent for fluorescence imaging of the treatment response in prostate cancer.

Xu, Hongchuang; Wang, Yanpu; Zhang, Jingming; Duan, Xiaojiang; Zhang, Ting; Cai, Xuekang; Ha, Hyunsoo; Byun, Youngjoo et al. · Eur J Nucl Med Mol Imaging · 2022

basic_science · Level V

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Abstract

Radioligand therapy (RLT) targeting prostate-specific membrane antigen (PSMA) is emerging as an effective treatment option for metastatic castration-resistant prostate cancer (mCRPC). An imaging-based method to quantify early treatment responses can help to understand and optimize RLT. We developed a self-triggered probe 2 targeting the colocalization of PSMA and caspase-3 for fluorescence imaging of RLT-induced apoptosis. The probe binds to PSMA potently with a K<sub>i</sub> of 4.12 nM, and its fluorescence can be effectively switched on by caspase-3 with a K<sub>m</sub> of 67.62 μM. Cellular and in vivo studies demonstrated its specificity for imaging radiation-induced caspase-3 upregulation in prostate cancer. To identify the detection limit of our method, we showed that probe 2 could achieve 1.79 times fluorescence enhancement in response to <sup>177</sup>Lu-RLT in a medium PSMA-expressing 22Rv1 xenograft model. Probe 2 can potently bind to PSMA, and the fluorescence signal can be sensitively switched on by caspase-3 both in vitro and in vivo. This method may provide an effective tool to investigate and optimize PSMA-RLT.

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