Liang Sihao, Hou Peng, Wang Xuezhu, Liang Wanmei, Zhong Shaonan, Zhao Ruiyue, Ke Miao, Li Youcai, Fu Yimin, Zhong Huizhen, Sun Chang, Li Hanzhao, Guo Daxin, Liu Yunqi, Wang Xinlu
Department of Nuclear Medicine, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Shanghai United Imaging Healthcare Advanced Technology Research Institute, Shanghai, China.
JACC Cardiovasc Imaging. 2025 Sep;18(9):997-1009. doi: 10.1016/j.jcmg.2025.05.021. Epub 2025 Jul 30.
Myocardial fibrosis (MF) is a key pathophysiological characteristic of dilated cardiomyopathy (DCM). Radiolabeled imaging agents targeting fibroblast activation protein (FAP) enhance the accuracy and sensitivity for detecting early-stage myocardial fibrosis.
This study aimed to evaluate the feasibility of using F-labeled FAP inhibitor tracer (FAPI-42) positron emission tomography (PET) imaging for detecting myocardial fibroblast activation and fibrosis in DCM patients.
In total, 19 DCM patients underwent F-FAPI-42 PET/computed tomography imaging, with 14 also underwent cardiac PET/cardiac magnetic resonance (CMR). Four patients underwent cardiac transplantation within 9 to 124 days after PET scans. Control groups were enrolled to establish the normal range of F-FAPI activity and CMR parameters. Spearman correlation analysis assessed correlations between F-FAPI uptake, the degree of collagen fiber deposition and FAP fluorescence, cardiac function parameters obtained from echocardiography, and PET/CMR.
F-FAPI PET imaging revealed varying degrees of FAPI uptake across diverse regions of the myocardium in DCM patients, significantly higher than the control group. F-FAPI-42 PET identified more abnormal segments (n = 168) than CMR-LGE (n = 95). Furthermore, in FAPI-positive segments, the T-postcontrast values and extracellular volume % were higher than in FAPI-negative segments (n = 56). Additionally, the myocardial long-axis radial PS% capacity was more severely impaired. In heart transplant patients, the FAPI uptake strongly correlated with FAP mean fluorescence intensity (P < 0.001) and collagen fiber deposition (P < 0.05). The FAPI uptake also correlated with cardiac function parameters assessed by CMR (end-systolic volume, end-diastolic volume, left ventricular ejection fraction %, and extracellular volume %). As NYHA functional class progressed from Ⅱ to Ⅳ, metabolically active volume increased consistently. However, maximum standardized uptake value and total lesion FAPI initially increasing and then subsequently declining.
F-FAPI PET is capable of detecting fibroblast activation in the myocardium of DCM, strongly correlating with histological markers and cardiac function parameters. Metabolically active volume is an effective indicator for assessing the condition of DCM, whereas maximum standardized uptake value and total lesion FAPI may potentially offer prognosis values.
心肌纤维化（MF）是扩张型心肌病（DCM）的关键病理生理特征。靶向成纤维细胞活化蛋白（FAP）的放射性标记成像剂提高了检测早期心肌纤维化的准确性和敏感性。
本研究旨在评估使用F标记的FAP抑制剂示踪剂（FAPI-42）正电子发射断层扫描（PET）成像检测DCM患者心肌成纤维细胞活化和纤维化的可行性。
总共19例DCM患者接受了F-FAPI-42 PET/计算机断层扫描成像，其中14例还接受了心脏PET/心脏磁共振成像（CMR）。4例患者在PET扫描后9至124天内接受了心脏移植。纳入对照组以确定F-FAPI活性和CMR参数的正常范围。Spearman相关性分析评估F-FAPI摄取、胶原纤维沉积程度和FAP荧光、超声心动图获得的心脏功能参数以及PET/CMR之间的相关性。
F-FAPI PET成像显示DCM患者心肌不同区域有不同程度的FAPI摄取，显著高于对照组。F-FAPI-42 PET识别出的异常节段（n = 168）比CMR-LGE（n = 95）更多。此外，在FAPI阳性节段，对比剂后T值和细胞外容积百分比高于FAPI阴性节段（n = 56）。另外，心肌长轴径向PS%容量受损更严重。在心脏移植患者中，FAPI摄取与FAP平均荧光强度（P < 0.001）和胶原纤维沉积（P < 0.05）密切相关。FAPI摄取还与CMR评估的心脏功能参数（收缩末期容积、舒张末期容积、左心室射血分数%和细胞外容积%）相关。随着纽约心脏协会（NYHA）心功能分级从Ⅱ级进展到Ⅳ级，代谢活跃容积持续增加。然而，最大标准化摄取值和总病变FAPI最初增加，随后下降。
F-FAPI PET能够检测DCM患者心肌中的成纤维细胞活化，与组织学标志物和心脏功能参数密切相关。代谢活跃容积是评估DCM病情的有效指标，而最大标准化摄取值和总病变FAPI可能具有预后价值。
