A self‑triggered radioligand therapy agent for fluorescence imaging of the treatment response in prostate cancer
A self‑triggered radioligand therapy agent for fluorescence imaging of the treatment response in prostate cancer
复制标题
用于前列腺癌治疗反应荧光成像的自触发放射配体治疗剂
DOI：
10.1007/s00259-022-05743-7
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发表时间：
2022
影响因子：
9.1
通讯作者：
Xing Yang
中科院分区：
文献类型：
--
作者：
Hongchuang Xu;Yanpu Wang;Jingming Zhang;Xiaojiang Duan;Ting Zhang;Xuekang Cai;Hyunsoo Ha;Youngjoo Byun;Yan Fan;Zhi Yang;Yiguang Wang;Zhaofei Liu;Xing Yang
目的以前列腺特异性膜抗原（PSMA）为靶点的放射配体治疗（RLT）是治疗转移性去势抵抗性前列腺癌（mCRPC）的有效方法。一种基于成像的方法来量化早期治疗反应可以帮助理解和优化RLT.MethodsWe开发了一种自触发探针2，靶向PSMA和caspase-3的共定位，用于RLT诱导的凋亡的荧光成像。细胞和体内研究表明，其特异性成像辐射诱导的caspase-3在前列腺癌的上调。结论探针2能有效地与PSMA结合，且在体内外均能被caspase-3敏感地激活荧光信号。该方法为研究和优化PSMA-RLT提供了一种有效的工具。
PurposeRadioligand 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.MethodsWe developed a self-triggered probe2targeting the colocalization of PSMA and caspase-3 for fluorescence imaging of RLT-induced apoptosis.ResultsThe probe binds to PSMA potently with aKiof 4.12 nM, and its fluorescence can be effectively switched on by caspase-3 with aKmof 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 to177Lu-RLT in a medium PSMA-expressing 22Rv1 xenograft model.ConclusionProbe2can 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.