Audi Said, Poellmann Michael, Zhu Xiaoguang, Li Zhixin, Zhao Ming
Department of Biomedical Engineering, Marquette University, Milwaukee, WI, USA.
Nucl Med Biol. 2007 Nov;34(8):897-905. doi: 10.1016/j.nucmedbio.2007.06.009. Epub 2007 Sep 4.
It was recently demonstrated that the radiolabeled C2A domain of synaptotagmin I accumulates avidly in the area at risk after ischemia and reperfusion. The objective was to quantitatively characterize the dynamic uptake of radiolabeled C2A in normal and ischemically injured myocardia using a compartmental model.
To induce acute myocardial infarction, the left descending coronary artery was ligated for 18 min, followed by reperfusion. [99mTc]C2A-GST or its inactivated form, [99mTc]C2A-GST-NHS, was injected intravenously at 2 h after reperfusion. A group of four rats was sacrificed at 10, 30, 60 and 180 after injection. Uptake of [99mTc]C2A-GST and [99mTc]C2A-GST-NHS in the area at risk and in the normal myocardium were determined by gamma counting. A compartmental model was developed to quantitatively interpret myocardial uptake kinetic data. The model consists of two physical spaces (vascular space and tissue space), with plasma activity as input. The model allows for [99mTc]C2A-GST and [99mTc]C2A-GST-NHS diffusion between vascular and tissue spaces, as well as for [99mTc]C2A-GST sequestration in vascular and tissue spaces via specific binding.
[99mTc]C2A-GST uptake in the area at risk was significantly higher than that for [99mTc]C2A-GST-NHS at all time points. The compartmental model separated [99mTc]C2A-GST uptake in the area at risk due to passive retention from that due to specific binding. The maximum amount of [99mTc]C2A-GST that could be sequestered in the area at risk due to specific binding was estimated at a total of 0.048 nmol/g tissue. The rate of [99mTc]C2A-GST sequestration within the tissue space of the area at risk was 0.012 ml/min. Modeling results also revealed that the diffusion rate of radiotracer between vascular and tissue spaces is the limiting factor of [99mTc]C2A-GST sequestration within the tissue space of the area at risk.
[99mTc]C2A-GST is sequestered in the ischemically injured myocardium in a well-defined dynamic profile. Model parameters will be valuable indicators for gauging and guiding the development of future-generation molecular probes.
最近有研究表明，放射性标记的突触结合蛋白I的C2A结构域在缺血再灌注后的危险区域大量聚集。本研究旨在使用房室模型定量描述放射性标记的C2A在正常和缺血损伤心肌中的动态摄取情况。
为诱导急性心肌梗死，结扎左冠状动脉前降支18分钟，随后进行再灌注。在再灌注后2小时静脉注射[99mTc]C2A-GST或其失活形式[99mTc]C2A-GST-NHS。在注射后10、30、60和180分钟处死一组4只大鼠。通过γ计数法测定危险区域和正常心肌中[99mTc]C2A-GST和[99mTc]C2A-GST-NHS的摄取情况。建立房室模型以定量解释心肌摄取动力学数据。该模型由两个物理空间（血管空间和组织空间）组成，以血浆活性作为输入。该模型允许[99mTc]C2A-GST和[99mTc]C2A-GST-NHS在血管和组织空间之间扩散，以及[99mTc]C2A-GST通过特异性结合在血管和组织空间中滞留。
在所有时间点，危险区域中[99mTc]C2A-GST的摄取均显著高于[99mTc]C2A-GST-NHS。房室模型将危险区域中[99mTc]C2A-GST由于被动滞留和特异性结合而产生的摄取区分开来。由于特异性结合，危险区域中可滞留的[99mTc]C2A-GST的最大量估计为0.048 nmol/g组织。危险区域组织空间内[99mTc]C2A-GST的滞留速率为0.012 ml/分钟。建模结果还表明，放射性示踪剂在血管和组织空间之间的扩散速率是危险区域组织空间内[99mTc]C2A-GST滞留的限制因素。
[99mTc]C2A-GST以明确的动态模式滞留在缺血损伤的心肌中。模型参数将成为衡量和指导下一代分子探针开发的有价值指标。
