Advancements in precision medicine necessitate understanding drug clearance pathways, especially in organs like the liver and kidneys. Traditional techniques such as PET/CT pose radiation hazards, whereas optical imaging poses challenges in maintaining both depth penetration and high resolution. Moreover, very few longitudinal studies have been performed for drug candidates for different symptoms. Leveraging non-ionizing photoacoustic tomography for deep tissue imaging, we developed a spatiotemporally resolved clearance pathway tracking (SRCPT) method, providing unprecedented insights into drug clearance dynamics within vital organs. SRCPT addresses challenges like laser fluence attenuation, enabling dynamic visualization of drug clearance pathways and essential parameter extraction. We employed a novel frequency component selection based synthetic aperture focusing technique (FCS-SAFT) with respiratory-artifacts-free weighting factors to enhance three-dimensional imaging resolutions. Inspired by this, we investigated the clearance pathway of a clinical drug, mitoxantrone, revealing reduced liver clearance when hepatic function is impaired. Furthermore, immunoglobulin G clearance analysis revealed significant differences among mice with varying renal injury degrees. The accuracy of our method was validated using a double-labeled probe [⁶⁸Ga]DFO-IRDye800CW, showing a strong positive correlation between SRCPT and PET. We believe that this powerful SRCPT promises precise mapping of drug clearance pathways and enhances diagnosis and treatment of liver and kidney-related diseases.

精准医学的进步需要了解药物清除途径，尤其是在肝脏和肾脏等器官中。PET/CT 等传统技术会带来辐射危害，而光学成像在保持深度穿透和高分辨率方面存在挑战。此外，对针对不同症状的候选药物进行的纵向研究很少。利用非电离光声断层扫描进行深层组织成像，我们开发了一种时空分辨清除途径跟踪 （SRCPT） 方法，为重要器官内的药物清除动力学提供了前所未有的见解。SRCPT 解决了激光通量衰减等挑战，实现了药物清除途径的动态可视化和基本参数提取。我们采用了一种基于频率分量选择的新型合成孔径聚焦技术 （FCS-SAFT），具有无呼吸伪影的加权因子来提高三维成像分辨率。受此启发，我们研究了临床药物米托蒽醌的清除途径，揭示了当肝功能受损时肝脏清除率降低。此外，免疫球蛋白 G 清除率分析显示不同肾损伤程度的小鼠之间存在显著差异。使用双标记探针 [⁶⁸Ga]DFO-IRDye800CW 验证了我们方法的准确性，显示 SRCPT 和 PET 之间具有很强的正相关性。我们相信，这种强大的 SRCPT 有望精确定位药物清除途径，并增强肝脏和肾脏相关疾病的诊断和治疗。