^(99)Tc^m-3PEG4-RGD用于家兔易损斑块分子显像

^(99)Tc^m-3PEG4-RGD for molecular imaging of vulnerable plaques in rabbits

目的探讨通过探测兔新生微血管活体评价动脉易损斑块的可行性。方法将15只雄性新西兰大白兔随机分成普食对照组(A组)、易损斑块组(B组)和稳定斑块组(C组),每组5只。于喂养2周后分别进行股动脉分离假手术(A、C组)和腹主动脉球囊拉伤术(B组),之后喂养不同成分饲料。于4、8、12周末静脉注射99 Tcm-3PEG4-RGD,注射后0.5h、1h、2h行SPECT/CT显像及同机CT平扫。4、8周末显像后对3组各处死1只实验兔,12周末处死剩余动物,行离体血管SPECT显像、病理及免疫组化染色分析。结果 3组实验兔注射99 Tcm-3PEG4-RGD后0.5hSPECT/CT图像显示,4周后3组兔腹主动脉区均未见放射性摄取增高,T/NT值差异无统计学意义(F=2.515,P=0.122);8周后B、C组局部放射性摄取增高(F=17.037,P=0.001);12周后B组腹主动脉局部放射性摄取明显高于A、C组(F=43.710,P<0.001)。8、12周末,B、C组腹主动脉中均含有新生微血管,且B组数量明显高于C组。B组兔腹主动脉斑块的AHA动脉粥样硬化分型为Ⅲ型及Ⅳ型,C组为AHAⅡ型。A组腹主动脉中无新生微血管及易损斑块。结论 99 Tcm-3PEG4-RGD分子显像对无创性评价兔动脉斑块稳定性具有一定价值。

Objective To evaluate the feasibility of ^99Tcm-3PEG4-RGD targeted to micro-vessels for detecting vulnerable plaque on rabbits with SPECT/CT imaging. Methods A total of 15 male New Zealand white rabbits were randomly divided into normal diet group （group A, n=5）, vulnerable plaque group （group B, n： 5） and stable plaque group （group C, n= 5）. The animals were given sham operation separating femoral artery （group A, C） or abdominal aorta balloon injury （group B） 2 weeks after feeding. ^99Tcm-3PEG4-RGD was injected at the end of the 4, 8 and 12 week. SPECT/CT images were captured 0.5, 1 and 2 h after injection. One rabbit was executed at the end of the 4 and 8 week, and the rest were executed at the end of the 12 week in each group, and then vitro SPECT imaging, pathology and immunohistochemistry analysis were performed. Results At the end of the 4 week, no uptake in aorta was observed in all 3 groups, and the difference of target/non-target ratio （T/NT） was not significant among 3 groups 0.5 h after injection （F=2. 515, P=0. 122）. At the end of the 8 week, there was certain radioactive uptake in group B and group C （F= 17. 037, P=0. 001）. At the end of the 12 week, the uptake in group B was much higher than that in group A and group C （F=43. 710, P〈0. 001）. The amount of micro-vessels in group B was significantly higher than that in group C. Histopathology results showed that at the end of the 12 week, AHA atherosclerotic type of rabbits in group B was type]Ⅲ and Ⅳ, while was typeⅡ in group C. There was no vulnerable plaque nor micro-vessels in rabbits of group A. Conclusion ^99 Tcm-3PEG4-RGD has certain value for noninvasively evaluating the stability of arterial plaque in rabbits.