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SPECT imaging of fibrin using fibrina??binding peptides

机译：使用血纤蛋白结合肽对血纤蛋白进行SPECT成像

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Noninvasive detection of fibrin in vivo using diagnostic imaging modalities may improve clinical decisiona??making on possible therapeutic options in atherosclerosis, cancer and thrombusa??related pathologies such as pulmonary embolism and deep venous thrombosis. The aim of this study was to assess the potential of a novel 111Ina??labeled fibrina??binding peptide (FibPep) to visualize thrombi in mice noninvasively using singlea??photon emission computed tomography (SPECT). FibPep and a negative control peptide (NCFibPep) were synthesized and their fibrina??binding properties were assessed in vitro. FibPep showed enhanced binding compared with NCFibPep to both fibrin and blood clots. FibPep bound to fibrin with a dissociation constant (Kd) of 0.8 ?? m, whereas NCFibPep displayed at least a 100a??fold lower affinity towards fibrin. A FeCl3a??injury carotid artery thrombosis mouse model was used to evaluate the peptides in vivo. FibPep and NCFibPep displayed rapid blood clearance and were eliminated via the renal pathway. In vivo SPECT imaging using FibPep allowed clear visualization of thrombi. Ex vivo biodistribution showed significantly increased uptake of FibPep in the thrombusa??containing carotid in comparison to the noninjured carotid (5.7a???±a??0.7 and 0.6a???±a??0.4% injected dose per gram (%ID ga??1), respectively; pa??a??0.01; na??=a??4), whereas nonspecific NCFibPep did not (0.4a???±a??0.2 and 0.3a???±a??0.0%ID ga??1, respectively; na??=a??4). In conclusion, FibPep displayed high affinity towards fibrin in vitro and rapid blood clearance in vivo, and allowed sensitive detection of thrombi using SPECT imaging. Therefore, this particular imaging approach may provide a new tool to diagnose and monitor diseases such as atherosclerosis and cancer. Copyright ?? 2013 John Wiley & Sons, Ltd.
机译：使用诊断性成像方式在体内进行非侵入性纤维蛋白检测可以改善在动脉粥样硬化，癌症和血栓相关疾病（如肺栓塞和深静脉血栓形成）中可能的治疗选择的临床决策。这项研究的目的是评估一种新的111Ina标记的纤维蛋白结合肽（FibPep）使用单子Δ光子发射计算机断层扫描（SPECT）无创地观察小鼠血栓的潜力。合成了FibPep和阴性对照肽（NCFibPep），并在体外评估了它们的纤维蛋白结合特性。与NCFibPep相比，FibPep与纤维蛋白和血凝块的结合增强。 FibPep与纤维蛋白结合，解离常数（Kd）为0.8 ?? m，而NCFibPep对血纤蛋白的亲和力至少低100a -1倍。用FeCl3a14损伤颈动脉血栓形成小鼠模型评价体内肽。 FibPep和NCFibPep显示出快速的血液清除，并通过肾脏途径清除。使用FibPep进行的体内SPECT成像可清晰显示血栓。与未损伤的颈动脉相比，离体生物分布显示含血栓的颈动脉中FibPep的摄取显着增加（每克注射剂量为5.7a-±a-0.7和0.6a-±a-0.4％（每克（分别为％ID ga ?? 1 ?? 1; pa ?? ?? 0.01; na ?? = a ?? 4），而非特异性NCFibPep没有（0.4a ??±a ?? 0.2和0.3a ?? 1）。分别为α±a≤0.0％ID gaθ1; naθ= aθ4）。总之，FibPep在体外显示出对血纤蛋白的高度亲和力，并在体内迅速清除血液，并允许使用SPECT成像灵敏地检测血栓。因此，这种特殊的成像方法可以提供一种新的工具来诊断和监测诸如动脉粥样硬化和癌症的疾病。版权?? 2013 John Wiley＆Sons，Ltd.

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