Institute for Biological and Medical Imaging, Helmholtz Zentrum Munich, Technical University Munich, Munich, Germany.
PLoS One. 2012;7(1):e30491. doi: 10.1371/journal.pone.0030491. Epub 2012 Jan 25.
The characterization of pharmacokinetic and biodistribution profiles is an essential step in the development process of new candidate drugs or imaging agents. Simultaneously, the assessment of organ function related to the uptake and clearance of drugs is of great importance. To this end, we demonstrate an imaging platform capable of high-rate characterization of the dynamics of fluorescent agents in multiple organs using multispectral optoacoustic tomography (MSOT). A spatial resolution of approximately 150 µm through mouse cross-sections allowed us to image blood vessels, the kidneys, the liver and the gall bladder. In particular, MSOT was employed to characterize the removal of indocyanine green from the systemic circulation and its time-resolved uptake in the liver and gallbladder. Furthermore, it was possible to track the uptake of a carboxylate dye in separate regions of the kidneys. The results demonstrate the acquisition of agent concentration metrics at rates of 10 samples per second at a single wavelength and 17 s per multispectral sample with 10 signal averages at each of 5 wavelengths. Overall, such imaging performance introduces previously undocumented capabilities of fast, high resolution in vivo imaging of the fate of optical agents for drug discovery and basic biological research.
药物代谢动力学和生物分布特征的描述是新候选药物或成像剂开发过程中的一个重要步骤。同时,评估与药物摄取和清除相关的器官功能也非常重要。为此,我们展示了一种成像平台,该平台能够使用多光谱光声断层扫描(MSOT)高速描述多个器官中荧光剂的动力学特征。通过对小鼠横截面进行约 150µm 的空间分辨率,可以对血管、肾脏、肝脏和胆囊进行成像。特别是,MSOT 被用于描述从体循环中去除吲哚菁绿及其在肝脏和胆囊中的时间分辨摄取。此外,还可以追踪肾脏不同区域中羧酸染料的摄取。研究结果表明,在单个波长下以每秒 10 个样本的速率,在 17 秒内以每秒 10 个信号平均值获得 5 个波长的多光谱样本,获得了代理浓度指标。总的来说,这种成像性能为药物发现和基础生物学研究中光学试剂的命运的快速、高分辨率体内成像引入了以前未记录的能力。