Photophysical Tuning of N-Oxide-Based Probes Enables Ratiometric Photoacoustic Imaging of Tumor Hypoxia
Photophysical Tuning of N-Oxide-Based Probes Enables Ratiometric Photoacoustic Imaging of Tumor Hypoxia
复制标题
DOI：
10.1021/acschembio.8b00099
复制
发表时间：
2018-07-01
影响因子：
4
通讯作者：
Chan, Jefferson
中科院分区：
文献类型：
--
作者：
Knox, Hailey J.;Kim, Tae Wook;Chan, Jefferson
当快速生长的肿瘤的氧气供应变得不足以支持各种生理过程时，就会产生缺氧。这在肿瘤转移和治疗耐药中起着重要作用。因此，识别肿瘤缺氧可以指导治疗计划和预测患者的反应。然而，缺氧量不均匀地分布在整个肿瘤中，这使得精确定位它们成为一个挑战。在此，我们报道了比率式低氧探针1(rHyP-1)的研制，这是一种低氧响应的小分子探针，旨在利用光声成像可靠地检测低氧。光声成像利用近红外(NIR)光来诱导产生超声信号，从而能够在厘米深度获得高分辨率图像。结合rHyP-1的比率测量能力，可以以前所未有的空间分辨率进行可靠的缺氧检测，同时将与浓度依赖和组织异质性相关的误差降至最低。
Hypoxia results when the oxygen supply to rapidly growing tumors becomes inadequate to support various physiological processes. This plays a role in tumor metastasis and treatment resistance. Therefore, identifying tumor hypoxia can guide treatment planning and predict patient responses. However, hypoxic volumes are heterogeneously dispersed throughout a tumor, making it a challenge to pinpoint them with any degree of accuracy. Herein, we report the development of ratiometric hypoxia probe 1 (rHyP-1), which is a hypoxia-responsive small-molecule probe designed for reliable hypoxia detection using photoacoustic imaging. Photoacoustic imaging utilizes near-infrared (NIR) light to induce the production of ultrasound signals, enabling high-resolution image acquisition at centimeter depths. Together with the ratiometric capability of rHyP-1, reliable hypoxia detection with unprecedented spatial resolution is possible while minimizing error associated with concentration dependence and tissue heterogeneity.