INSERM, U698, Cardiovascular Bioengineering, Paris, France.
J Nucl Med. 2011 Sep;52(9):1433-40. doi: 10.2967/jnumed.110.085852. Epub 2011 Aug 17.
P-selectin expression is involved in the pathophysiology of biologically active arterial thrombus and endothelial activation after a transient ischemic event. Fucoidan is a polysaccharidic ligand of P-selectin, with a nanomolar affinity. In the present study, we propose a new approach of P-selectin molecular imaging based on radiolabeled fucoidan.
Two kinds of experimental models were selected to evaluate the ability of radiolabeled fucoidan to detect P-selectin expression: platelet-rich arterial thrombi (vegetations of infective endocarditis and arterial mural thrombus) and myocardial ischemia-reperfusion. These 2 settings were chosen because they were clinically relevant, and both were associated with an important overexpression of platelet and endothelial P-selectin, respectively.
(99m)Tc-fucoidan SPECT was able to detect the presence of platelet-rich arterial thrombi in all animals, with a median target-to-background ratio of 5.2 in vegetations of endocarditis and 3.6 in mural aneurysmal thrombus, and to detect a persistent endothelial activation at 2 h after reperfusion. In this latter model, the magnitude of the signal was correlated with the extent of myocardium that underwent transient ischemia. The sensitivity of selectivity of the uptake and retention of (99m)Tc-fucoidan in both settings was excellent.
This study supports (99m)Tc-fucoidan as a relevant imaging agent for in vivo detection of biologic activities associated with P-selectin overexpression, such as arterial thrombus and ischemic memory. Given the reported wide availability at a low cost, and its low toxicity, fucoidan seems to overcome some of the limitations of previous P-selectin-targeted imaging agents.
P-选择素表达参与生物活性动脉血栓形成和短暂性缺血事件后内皮细胞激活的病理生理学过程。褐藻糖胶是 P-选择素的一种多糖配体，具有纳摩尔亲和力。在本研究中，我们提出了一种基于放射性标记褐藻糖胶的新的 P-选择素分子成像方法。
选择两种实验模型来评估放射性标记褐藻糖胶检测 P-选择素表达的能力：富含血小板的动脉血栓（感染性心内膜炎的赘生物和动脉壁血栓）和心肌缺血再灌注。选择这两种设置是因为它们具有临床相关性，并且分别与血小板和内皮 P-选择素的重要过表达相关。
(99m)Tc-褐藻糖胶 SPECT 能够在所有动物中检测到富含血小板的动脉血栓，在心内膜炎赘生物中的中位靶背比为 5.2，在壁动脉瘤血栓中的中位靶背比为 3.6，并在再灌注后 2 小时检测到持续的内皮激活。在后一种模型中，信号的幅度与经历短暂缺血的心肌范围相关。(99m)Tc-褐藻糖胶在这两种设置中的摄取和保留的敏感性和选择性都很好。
这项研究支持(99m)Tc-褐藻糖胶作为一种相关的成像剂，用于体内检测与 P-选择素过表达相关的生物活性，如动脉血栓形成和缺血记忆。鉴于其报道的广泛可用性、低成本和低毒性，褐藻糖胶似乎克服了以前 P-选择素靶向成像剂的一些局限性。
