Understanding the in vivo uptake kinetics of a phosphatidylethanolamine-binding agent (99m)Tc-Duramycin.
Understanding the in vivo uptake kinetics of a phosphatidylethanolamine-binding agent (99m)Tc-Duramycin.
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DOI：
10.1016/j.nucmedbio.2012.02.004
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发表时间：
2012-08
影响因子：
3.1
通讯作者：
Zhao M
中科院分区：
文献类型：
--
作者：
Audi S;Li Z;Capacete J;Liu Y;Fang W;Shu LG;Zhao M
99mTc-Duramycin是一种基于肽的分子探针，可特异性结合磷脂酰乙醇胺（PE）。目的是表征99mTc-Duramycin与靶组织之间分子相互作用的动力学。Sprague Dawley大鼠心肌缺血（30min）和再灌注（120min）诱导心肌组织高水平可及性PE。利用SPECT/CT捕捉99mTc-duramycin的靶结合和生物分布。为了量化结合动力学，在注射后3、10、20、60和180分钟，通过伽马计数测量缺血与正常心脏组织中放射性的存在。99mTc-Duramycin的部分灭活形式以相同的方式进行分析。建立了一个室室模型来量化99mTc-Duramycin在正常和缺血心肌组织中的摄取动力学。99mTc-duramycin以高靶本底放射强度与受损组织紧密结合。室室模型显示心肌组织中结合位点对99mTc-Duramycin的可及性不是限制因素，靶组织中靶结合的速率常数为2.2 ml/nmol/min/g。缺血心肌中99mTc-Duramycin的可用结合位点数估计为0.14 nmol/g。D15的共价修饰导致其结合亲和力降低了9倍。mtc - duramycin以pe依赖的方式在靶组织中迅速积累。模型结果反映了一种有效的摄取机制，这与放射性药物的低分子量和相对较高的可用结合位点密度相一致。这些数据有助于更好地定义99mTc-Duramycin作为一种新型pe结合剂的成像效用。
99mTc-Duramycin is a peptide-based molecular probe that binds specifically to phosphatidylethanolamine (PE). The goal was to characterize the kinetics of molecular interactions between 99mTc-Duramycin and the target tissue. High level of accessible PE is induced in cardiac tissues by myocardial ischemia (30 min) and reperfusion (120 min) in Sprague Dawley rats. Target binding and biodistribution of 99mTc-duramycin was captured using SPECT/CT. To quantify the binding kinetics, the presence of radioactivity in ischemic versus normal cardiac tissues was measured by gamma counting at 3, 10, 20, 60 and 180 min after injection. A partially inactivated form of 99mTc-Duramycin was analyzed in the same fashion. A compartment model was developed to quantify the uptake kinetics of 99mTc-Duramycin in normal and ischemic myocardial tissue. 99mTc-duramycin binds avidly to the damaged tissue with a high target-to-background radio. Compartment modeling shows that accessibility of binding sites in myocardial tissue to 99mTc-Duramycin is not a limiting factor and the rate constant of target binding in the target tissue is at 2.2 ml/nmol/min/g. The number of available binding sites for 99mTc-Duramycin in ischemic myocardium was estimated at 0.14 nmol/g. Covalent modification of D15 resulted in a 9 fold reduction in binding affinity. 99mTc-Duramycin accumulates avidly in target tissues in a PE-dependent fashion. Model results reflect an efficient uptake mechanism, consistent with the low molecular weight of the radiopharmaceutical and the relatively high density of available binding sites. These data help better define the imaging utilities of 99mTc-Duramycin as a novel PE-binding agent.
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DOI：
10.1016/0735-1097(93)90253-w
发表时间：
1993-04-01
影响因子：
24
作者：
FARB, A;KOLODGIE, FD;VIRMANI, R
通讯作者：
VIRMANI, R
影响因子：
82.9
作者：
Zhao, M;Beauregard, DA;Brindle, KM
通讯作者：
Brindle, KM
DOI：
10.1016/0005-2736(88)90557-3
发表时间：
1988-08-18
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
POST, JA;LANGER, GA;VERKLEIJ, AJ
通讯作者：
VERKLEIJ, AJ
影响因子：
4.8
作者：
Emoto, K;Inadome, H;Umeda, M
通讯作者：
Umeda, M
影响因子：
3.2
作者：
Waehrens, Lasse N.;Heegaard, Christian W.;Rasmussen, Jan T.
通讯作者：
Rasmussen, Jan T.