Strauss H William, Mari Carina, Patt Bradley E, Ghazarossian Vartan
Section of Nuclear Medicine, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA.
J Am Coll Cardiol. 2006 Apr 18;47(8 Suppl):C97-100. doi: 10.1016/j.jacc.2005.11.051.
An intravascular catheter was developed to identify inflammation in coronary atheroma. Inflammation in atheroma is associated with large numbers of macrophages. These cells have increased metabolism, increased expression of chemotactic receptors, and a high frequency of apoptosis-associated phosphatidylserine expression. Each of these parameters can be identified in vivo using specific radiolabeled agents: metabolism can be identified with 18F fluorodeoxyglucose (FDG), receptor expression with 99mTc monocyte chemotactic peptide-1, and apoptosis with 99mTc annexin V. The locally increased concentration of these tracers is readily demonstrable in experimental lesions by ex vivo autoradiography; however, the small lesion size makes it difficult to identify atheroma in the coronaries with conventional imaging equipment. In contrast, with a radiation-sensitive catheter, optimized to sense charged particle rather than gamma or x-radiation, specific lesions could be identified and localized. Charged particle radiation is emitted as a byproduct of nearly all radioactive decay but is typically most abundant in radionuclides that decay by beta emission (either positrons or negatrons). Prototype catheters, using a plastic scintillator mated to an optical fiber, have been tested in the laboratory with the positron-emitting radiopharmaceutical 18FDG. The catheter had sufficient sensitivity to detect lesions concentrating nanocurie concentrations of 18FDG. Ex vivo experiments in apo-e-/- mice confirmed the ability of the catheter to detect 18FDG in aortic lesions. These feasibility studies demonstrate the sensitivity of a beta-sensitive catheter system. Additional mechanical refinements are needed to optimize the system in anticipation of in vivo animal studies.
一种用于识别冠状动脉粥样硬化炎症的血管内导管被研发出来。动脉粥样硬化中的炎症与大量巨噬细胞有关。这些细胞代谢增加、趋化受体表达增加且凋亡相关磷脂酰丝氨酸表达频率较高。这些参数中的每一个都可以在体内使用特定的放射性标记剂来识别:代谢可用18F氟脱氧葡萄糖(FDG)识别,受体表达可用99mTc单核细胞趋化肽-1识别,凋亡可用99mTc膜联蛋白V识别。通过离体放射自显影在实验性病变中很容易证明这些示踪剂的局部浓度增加;然而,病变尺寸较小使得用传统成像设备难以识别冠状动脉中的动脉粥样硬化。相比之下,使用经过优化以检测带电粒子而非伽马或X射线的辐射敏感导管,可以识别和定位特定病变。带电粒子辐射是几乎所有放射性衰变的副产品,但通常在通过β发射(正电子或负电子)衰变的放射性核素中最为丰富。使用与光纤配合的塑料闪烁体的原型导管已在实验室中用发射正电子的放射性药物氟代脱氧葡萄糖进行了测试。该导管具有足够的灵敏度来检测聚集纳居里浓度氟代脱氧葡萄糖的病变。在载脂蛋白E基因敲除小鼠中进行的离体实验证实了该导管在主动脉病变中检测氟代脱氧葡萄糖的能力。这些可行性研究证明了β敏感导管系统的灵敏度。为了预期进行体内动物研究,需要进行额外的机械改进以优化该系统。