Dynamic synthetic-scanning photoacoustic tracking monitors hepatic and renal clearance pathway of exogeneous probes in vivo

IF 3.5 3区 医学 Q2 CHEMISTRY, MEDICINAL ACS Medicinal Chemistry Letters Pub Date : 2024-10-31 DOI:10.1038/s41377-024-01644-6
Jing Lv, Hengrong Lan, Aoji Qin, Tong Sun, Dan Shao, Fei Gao, Junjie Yao, Kamran Avanaki, Liming Nie
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Abstract

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.

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动态合成扫描光声跟踪监测体内外源探针的肝脏和肾脏清除途径
精准医疗的发展要求了解药物清除途径,尤其是肝脏和肾脏等器官的清除途径。正电子发射计算机断层显像(PET/CT)等传统技术存在辐射危害,而光学成像在保持深度穿透和高分辨率方面也面临挑战。此外,针对不同症状的候选药物很少进行纵向研究。利用用于深部组织成像的非电离光声断层成像技术,我们开发了一种时空分辨清除路径跟踪(SRCPT)方法,为重要器官内的药物清除动态提供了前所未有的洞察力。SRCPT 解决了激光通量衰减等难题,实现了药物清除路径的动态可视化和基本参数提取。我们采用了一种新颖的基于频率成分选择的合成孔径聚焦技术(FCS-SAFT)和无呼吸伪影加权因子,以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,发现当肝功能受损时,肝脏的清除率会降低。此外,免疫球蛋白 G 清除率分析表明,不同肾损伤程度的小鼠之间存在显著差异。我们使用双标记探针[68Ga]DFO-IRDye800CW验证了我们方法的准确性,结果显示 SRCPT 和 PET 之间存在很强的正相关性。我们相信,这种功能强大的 SRCPT 可精确绘制药物清除途径图,提高肝肾相关疾病的诊断和治疗水平。
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来源期刊
ACS Medicinal Chemistry Letters
ACS Medicinal Chemistry Letters CHEMISTRY, MEDICINAL-
CiteScore
7.30
自引率
2.40%
发文量
328
审稿时长
1 months
期刊介绍: ACS Medicinal Chemistry Letters is interested in receiving manuscripts that discuss various aspects of medicinal chemistry. The journal will publish studies that pertain to a broad range of subject matter, including compound design and optimization, biological evaluation, drug delivery, imaging agents, and pharmacology of both small and large bioactive molecules. Specific areas include but are not limited to: Identification, synthesis, and optimization of lead biologically active molecules and drugs (small molecules and biologics) Biological characterization of new molecular entities in the context of drug discovery Computational, cheminformatics, and structural studies for the identification or SAR analysis of bioactive molecules, ligands and their targets, etc. Novel and improved methodologies, including radiation biochemistry, with broad application to medicinal chemistry Discovery technologies for biologically active molecules from both synthetic and natural (plant and other) sources Pharmacokinetic/pharmacodynamic studies that address mechanisms underlying drug disposition and response Pharmacogenetic and pharmacogenomic studies used to enhance drug design and the translation of medicinal chemistry into the clinic Mechanistic drug metabolism and regulation of metabolic enzyme gene expression Chemistry patents relevant to the medicinal chemistry field.
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