Folz Jeff, Eido Ahmad, Gonzalez Maria E, Caruso Roberta, Wang Xueding, Kleer Celina G, Jo Janggun
Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA.
Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Sensors (Basel). 2025 Jul 31;25(15):4724. doi: 10.3390/s25154724.
Elevated extracellular potassium (K) in the tumor microenvironment (TME) of breast and other cancers is increasingly recognized as a critical factor influencing tumor progression and immune suppression. Current methods for noninvasive mapping of the potassium distribution in tumors are limited. Here, we employed photoacoustic chemical imaging (PACI) with a solvatochromic dye-based, potassium-sensitive nanoprobe (SDKNP) to quantitatively visualize extracellular potassium levels in an orthotopic metaplastic breast cancer mouse model, Ccn6-KO. Tumors of three distinct sizes (5 mm, 10 mm, and 20 mm) were imaged using multi-wavelength photoacoustic imaging at five laser wavelengths (560, 576, 584, 605, and 625 nm). Potassium concentration maps derived from spectral unmixing of the photoacoustic images at the five laser wavelengths revealed significantly increased potassium levels in larger tumors, confirmed independently by inductively coupled plasma mass spectrometry (ICP-MS). The PACI results matched ICP-MS measurements, validating PACI as a robust, noninvasive imaging modality for potassium mapping in tumors . This work establishes PACI as a promising tool for studying the chemical properties of the TME and provides a foundation for future studies evaluating the immunotherapy response through ionic biomarker imaging.
乳腺癌和其他癌症的肿瘤微环境（TME）中细胞外钾（K）水平升高，越来越被认为是影响肿瘤进展和免疫抑制的关键因素。目前用于肿瘤中钾分布无创成像的方法有限。在这里，我们采用基于溶剂化显色染料的钾敏感纳米探针（SDKNP）的光声化学成像（PACI），在原位化生乳腺癌小鼠模型Ccn6-KO中定量可视化细胞外钾水平。使用五个激光波长（560、576、584、605和625 nm）的多波长光声成像对三种不同大小（5 mm、1０mm和20 mm）的肿瘤进行成像。通过对五个激光波长下光声图像的光谱解混得到的钾浓度图显示，较大肿瘤中的钾水平显著升高，这通过电感耦合等离子体质谱（ICP-MS）独立证实。PACI结果与ICP-MS测量结果相符，验证了PACI作为一种用于肿瘤中钾成像的强大无创成像方式。这项工作将PACI确立为研究TME化学性质的有前途的工具，并为未来通过离子生物标志物成像评估免疫治疗反应的研究提供了基础。
