美国伊利诺伊大学厄巴纳-香槟分校Chan, Jefferson团队报道了肺癌模型中谷胱甘肽升高的光声成像用于伴随诊断。相关研究成果于2021年10月25日发表在国际顶尖学术期刊《自然—化学》。

伴随诊断（CDx）是一种功能强大的检测手段，可为医生提供关键的生物标记物信息，通过将治疗与患者匹配来改善治疗效果。

该文中，研究人员报告了一种基于光声成像的CDx（PACDx），用于选择性检测肺癌模型中升高的谷胱甘肽（GSH）。GSH在大多数细胞中都很丰富，因此研究人员采用了物理-有机化学方法来精确调节反应性，以区分正常和病理状态。为了评估PACDx在体内的疗效，研究人员设计了一项盲法研究，其中光声成像用于识别携带异种肺移植物的小鼠。研究人员还在原位肺癌和肝转移模型中使用PACDx对GSH进行成像。

此外，研究人员还设计了一种匹配的前药PARx，它使用相同的SNAr化学反应释放具有集成PA读数的化疗药物。研究表明，在肺癌异种移植模型中，PARx可以抑制肿瘤生长而无脱靶毒性。

附：英文原文

Title: Photoacoustic imaging of elevated glutathione in models of lung cancer for companion diagnostic applications

Author: Lucero, Melissa Y., Chan, Jefferson

Issue&Volume: 2021-10-25

Abstract: Companion diagnostics (CDx) are powerful tests that can provide physicians with crucial biomarker information that can improve treatment outcomes by matching therapies to patients. Here, we report a photoacoustic imaging-based CDx (PACDx) for the selective detection of elevated glutathione (GSH) in a lung cancer model. GSH is abundant in most cells, so we adopted a physical organic chemistry approach to precisely tune the reactivity to distinguish between normal and pathological states. To evaluate the efficacy of PACDx in vivo, we designed a blind study where photoacoustic imaging was used to identify mice bearing lung xenografts. We also employed PACDx in orthotopic lung cancer and liver metastasis models to image GSH. In addition, we designed a matching prodrug, PARx, that uses the same SNAr chemistry to release a chemotherapeutic with an integrated PA readout. Studies demonstrate that PARx can inhibit tumour growth without off-target toxicity in a lung cancer xenograft model.

DOI: 10.1038/s41557-021-00804-0

Source: https://www.nature.com/articles/s41557-021-00804-0