FAPI分子影像在心脏压力超负荷-卸负荷过程中应用的动物实验研究  

Animal experimental study of FAPI molecular imaging in cardiac pressure overload-unloading process

作　　者：王国坤 杨亲亲 曾振宇 罗秀 梁思雨 左长京 程超 刘夙璇 Wang Guokun;Yang Qinqin;Zeng Zhenyu;Luo Xiu;Liang Siyu;Zuo Changjing;Cheng Chao;Liu Suxuan(Department of Cardiovascular Surgery,the First Affiliated Hospital(Changhai Hospital)of Naval Medical University,Shanghai 200433,China;Department of Nuclear Medicine,the First Affiliated Hospital(Changhai Hospital)of Naval Medical University,Shanghai 200433,China;Department of Cardiology,the First Affiliated Hospital(Changhai Hospital)of Naval Medical University,Shanghai 200433,China)

机构地区：[1]海军军医大学第一附属医院心外科,上海200433 [2]海军军医大学第一附属医院核医学科,上海200433 [3]海军军医大学第一附属医院心内科,上海200433

出　　处：《中华核医学与分子影像杂志》2024年第11期655-660,共6页Chinese Journal of Nuclear Medicine and Molecular Imaging

基　　金：国家自然科学基金(82370385);上海市卫生健康委员会新兴交叉领域研究专项(2022JC004)。

摘　　要：目的探讨^(68)Ga-成纤维细胞激活蛋白(FAP)抑制剂(FAPI)-04 PET显像在压力负荷心力衰竭治疗中的价值。方法通过腹主动脉缩窄(AAC)术构建压力负荷心力衰竭大鼠模型。将30只大鼠按照完全随机法分为AAC组、7 d腹主动脉去缩窄(rAAC)组和假手术(sham)组(每组10只),在AAC术后4、8周对3组大鼠行^(68)Ga-FAPI-04 PET/CT显像,并于术后8周时行心脏超声、病理和免疫组织化学检查。采用单因素方差分析、两独立样本t检验和Pearson相关分析处理数据。结果^(68)Ga-FAPI-04 PET/CT显像示术后4、8周时,3组大鼠心脏及肝脏靶/本底比间差异均有统计学意义(F值:2547.12、2041.71、462.65和1210.97,均P<0.001)。心脏超声显示术后8周时,3组大鼠心脏的左心室射血分数(LVEF)、左心室舒张末期内径(LVIDd)、左心室收缩末期内径(LVIDs)间差异均有统计学意义(F值:118.92、9.11和10.63,均P<0.01)。术后8周时处死大鼠,Masson染色显示rAAC组心脏、肝脏纤维化程度较AAC组明显改善,免疫组织化学检查显示rAAC组心脏、肝脏组织FAP的表达明显低于AAC组(t值:-11.27~-4.16,均P<0.01)。相关性分析显示,术后8周时,AAC组和rAAC组大鼠心脏FAPI摄取与肝脏FAPI摄取、LVIDd、LVIDs呈正相关,与LVEF呈负相关;心脏、肝脏的FAPI摄取与对应脏器的纤维化程度、FAP水平也呈正相关(r值:-0.89、-0.88、0.72~0.97,均P<0.05)。结论^(68)Ga-FAPI-04 PET/CT显像可以显示心力衰竭超负荷压力卸载后的心-肝纤维化改善过程,心肌FAPI摄取和心力衰竭改善程度密切相关。Objective To investigate the utility of^(68)Ga-fibroblast activation protein(FAP)inhibitor(FAPI)-04 PET imaging in assessing the therapeutic response in pressure overload-induced heart failure.Methods Rat models of pressure overload-induced heart failure were established by abdominal aortic constriction(AAC).Thirty rats were categorized into AAC group,7 days reverse AAC(rAAC)group,and sham operation(sham)group(n=10 per group)using completely random grouping method.All rats underwent^(68)Ga-FAPI-04 PET/CT imaging at 4 and 8 weeks after the ACC operation,while echocardiography,pathological examination,and immunohistochemical analysis were performed at 8 weeks postoperation.One-way analysis of variance,independent-sample t test and Pearson correlation analysis were used for data analysis.Results^(68)Ga-FAPI-04 PET/CT imaging showed that the target-to-background ratios of the heart and liver had significant differences among three groups both at 4 and 8 weeks postoperation(F values:2547.12,2041.71,462.65,1210.97,all P<0.001).Echocardiography revealed left ventricular ejection fraction(LVEF),left ventricular internal diameter at end-diastole(LVIDd),and left ventricular internal diameter at end-systole(LVIDs)in three groups at 8 weeks postoperation were significantly different(F values:118.92,9.11,10.63,all P<0.01).Rats were sacrificed at 8 weeks postoperation,and Masson staining showed that the fibrosis in the heart and liver of the rAAC group was significantly improved compared with that of the AAC group,and immunohistochemical analysis revealed significantly lower FAP levels in the heart and liver of the rAAC group compared with those of the AAC group(t values:from-11.27 to-4.16,all P<0.01).FAPI uptake in the heart of the AAC group and rAAC group at 8 weeks postoperation were significantly positively correlated with FAPI uptake in the liver,LVIDd and LVIDs,FAPI uptake in the heart was significantly negatively correlated with LVEF,and FAPI uptake in the heart and liver were significantly positively correlated with fi

关 键 词：心力衰竭 喹啉类 同位素标记 镓放射性同位素 正电子发射断层显像术 体层摄影术 X线计算机 大鼠 

分 类 号：R817.4[医药卫生—影像医学与核医学] R541.6[医药卫生—放射医学]