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A Renal-Clearable Activatable Molecular Probe for Fluoro-Photacoustic and Radioactive Imaging of Cancer Biomarkers
Small ( IF 13.3 ) Pub Date : 2022-06-20 , DOI: 10.1002/smll.202201334
Shenhua Li 1 , Qing Li 1 , Wan Chen 1 , Zhuorun Song 1 , Yi An 1 , Peixin Chen 2 , Yan Wu 1 , Guanglin Wang 1 , Yayi He 2 , Qingqing Miao 1
Affiliation  

In vivo simultaneous visualization of multiple biomarkers is critical to accurately diagnose disease and decipher fundamental processes at a certain pathological evolution, which however is rarely exploited. Herein, a multimodal activatable imaging probe (P-125I) is reported with activatable fluoro-photoacoustic and radioactive signal for in vivo imaging of biomarkers (i.e., hepsin and prostate-specific membrane antigen (PSMA)) associated with prostate cancer diagnosis and prognosis. P-125I contains a near-infrared (NIR) dye that is caged with a hepsin-cleavable peptide sequence and linked with a radiolabeled PSMA-targeted ligand (PSMAL). After systemic administration, P-125I actively targets the tumor site via specific recognition between PSMA and PSMAL moiety and in-situ generates of activated fluoro-photoacoustic signal after reacting with hepsin to release the free dye (uncaged state). P-125I achieves precisely early detection of prostate cancer and renal clearance to alleviate toxicity issues. In addition, the accumulated radioactive and activated photoacoustic signal of probe correlates well with the respective expression level of PSMA and hepsin, which provides valuable foreseeability for cancer progression and prognosis. Thus, this study presents a multimodal activatable probe for early detection and in-depth deciphering of prostate cancer.

中文翻译:

用于癌症生物标志物荧光光声和放射性成像的肾脏可清除激活分子探针

多个生物标志物的体内同时可视化对于准确诊断疾病和破译特定病理演变的基本过程至关重要,但很少被利用。本文报道了一种多模式可激活成像探针 (P - 125 I),它具有可激活的荧光光声和放射性信号,用于与前列腺癌诊断和预后相关的生物标志物(即 hepsin 和前列腺特异性膜抗原 (PSMA))的体内成像. P - 125 I 含有一种近红外 (NIR) 染料,该染料被 hepsin 可切割肽序列笼罩,并与放射性标记的 PSMA 靶向配体 (PSMAL) 连接。全身给药后,P- 125我通过 PSMA 和 PSMAL 部分之间的特异性识别主动靶向肿瘤部位,并在与 hepsin 反应释放游离染料(未封闭状态)后原位产生活化的荧光光声信号。P - 125 I 实现了前列腺癌的精确早期检测和肾脏清除,以减轻毒性问题。此外,探针累积的放射性和活化光声信号与 PSMA 和 hepsin 各自的表达水平具有很好的相关性,这为癌症的进展和预后提供了有价值的可预见性。因此,本研究提出了一种用于早期检测和深入破译前列腺癌的多模式可激活探针。
更新日期:2022-06-20
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