靶向TSPO分子探针^(18)F-FDPA和^(18)F-LW223用于兔腹主动脉粥样硬化易损斑块PET显像的对比研究

Comparative PET molecular imaging study of abdominal vulnerable atherosclerotic plaque with targeted TSPO molecular probes ^(18)F-FDPA and ^(18)F-LW223 in rabbit models

目的比较靶向相对分子质量1.8×10^(4)转位蛋白(TSPO)的分子探针N,N-二乙基-2-[2-(4-^(18)F-氟苯基)-5,7-二甲基吡唑[1,5-a]并嘧啶-3-基]乙酰胺(^(18)F-FDPA)和^(18)F-(R)-(N-仲丁基)-3-氟甲基-N-甲基-4-苯基喹啉-2-甲酰胺(LW223)用于探测兔腹主动脉粥样硬化易损斑块(VAP)的可行性和效能。方法选取9只健康新西兰大白兔,用完全随机法分为3组(每组3只):正常对照组(A组)、VAP组(B组)和VAP治疗组(C组),分别于造模后第12、16和24周末注射^(18)F-FDPA和^(18)F-LW223,并于注射后40~50 min行活体腹主动脉PET/CT和同机CT血管成像(CTA)。所有显像结束后,处死全部动物,行腹主动脉病理学及免疫荧光检测。采用重复测量方差分析(Bonferroni法)和配对t检验分析数据。结果^(18)F-FDPA在3组不同时间点(第12、16和24周末)PET/CTA同机显像中,靶本比(TBR;腹主动脉病灶/左心室血池)值间差异均有统计学意义(F值:68.09~144.88,均P<0.001)。在第12周末显像中,3组腹主动脉区域均无明显显像剂摄取增高灶。在第16和24周末显像中,B组腹主动脉局部的摄取均高于同期时间点的C组(均P<0.05)和A组(均P<0.001);C组腹主动脉局部的摄取高于同期时间点的A组(均P<0.01)。3组不同时间点PET/CTA图像中,腹主动脉区域均无明显^(18)F-LW223摄取增高灶。在上述3个不同时间点,3组^(18)F-FDPA和^(18)F-LW223的TBR值间差异均有统计学意义(t值:2.88~36.79,均P<0.05)。病理HE、免疫荧光CD68和TSPO染色显示,B组^(18)F-FDPA高摄取易损斑块处巨噬细胞浸润数量多于C组。结论与^(18)F-LW223相比,^(18)F-FDPA可用于早期探测兔腹主动脉易损斑块,并可评估降脂药物干预后易损斑块稳定性的变化。

ObjectiveTo compare the feasibility and efficacy of translocator protein(TSPO)molecular probes N,N-diethyl-2-(2-(4-^(18)F-fluorophenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-yl)acetamide(^(18)F-FDPA)and ^(18)F-(R)-(N-sec-butyl)-3-fluoromethyl-N-methyl-4-phenylquinoline-2-carboxamide(LW223)for the detection of abdominal vulnerable atherosclerotic plaques(VAP)in rabbit models.MethodsNine healthy New Zealand white rabbits were divided into group A(control group,n=3),group B(VAP group,n=3)and group C(VAP treatment group,n=3)using completely randomized design.Animals were injected with ^(18)F-FDPA and ^(18)F-LW223 at the end of 12,16 and 24 weeks.PET/CT and CT angiography(CTA)was performed 40-50 min post injection.All rabbits were sacrificed at the end of 24 weeks after imaging studies.All abdominal aortas were collected for pathological and immunofluorescence examination.Repeated measures analysis of variance(Bonferroni test)and paired t-test were used to analyze the data.ResultsTarget-to-background ratio(TBR;abdominal aortic lesion/left ventricular blood pool)values of ^(18)F-FDPA in 3 groups at the end of 12,16 and 24 weeks were significantly different(F values:68.09-144.88,all P<0.001).At the end of 12 weeks,there was no increased uptake of ^(18)F-FDPA in the abdominal aorta region in 3 groups.The local ^(18)F-FDPA uptake of the abdominal aorta in group B was significantly higher than the uptake in group C and that in group A at the end of 16 and 24 weeks(P<0.05 or P<0.001),and there were significant differences between group C and group A,with higher uptake in group C(both P<0.01).In 3 groups,there was no significant ^(18)F-LW223 uptake in the abdominal aorta region at 3 time points of PET/CTA imaging.At the end of 12,16 and 24 weeks,TBR values of ^(18)F-FDPA and ^(18)F-LW223 in 3 groups exhibited statistical differences(t values:2.88-36.79,all P<0.05).HE,immunofluorescent CD68 and TSPO staining showed more macrophage infiltration in group B than group C.Conclusion ^(18)F-FDPA can be used to detect VAP in rabbits′abdominal arteries at early time compared to ^(18)F-LW223,and to evaluate the changes in the stability of vulnerable plaque after lipid-lowering drug intervention.