Heart failure remains a major source of late morbidity and mortality after myocardial infarction (MI). The temporospatial presence of activated fibroblasts in the injured myocardium predicts the quality of cardiac remodeling after MI. Therefore, monitoring of activated fibroblasts is of great interest for studying cardiac remodeling after MI. Fibroblast activation protein (FAP) expression is upregulated in activated fibroblasts. This study investigated the feasibility of imaging activated fibroblasts with a new ⁶⁸Ga-labeled FAP inhibitor (⁶⁸Ga-FAPI-04) for PET imaging of fibroblast activation in a preclinical model of MI. Methods: MI and sham-operated rats were scanned with ⁶⁸Ga-FAPI-04 PET/CT (1, 3, 6, 14, 23, and 30 d after MI) and with ¹⁸F-FDG (3 d after MI). Dynamic ⁶⁸Ga-FAPI-04 PET and blocking studies were performed on MI rats 7 d after coronary ligation. After in vivo scans, the animals were euthanized and their hearts harvested for ex vivo analyses. Cryosections were prepared for autoradiography, hematoxylin and eosin (H&E), and immunofluorescence staining. Results: ⁶⁸Ga-FAPI-04 uptake in the injured myocardium peaked on day 6 after coronary ligation. The tracer accumulated intensely in the MI territory, as identified by decreased ¹⁸F-FDG uptake and confirmed by PET/MR and H&E staining. Autoradiography and H&E staining of cross-sections revealed that ⁶⁸Ga-FAPI-04 accumulated mainly at the border zone of the infarcted myocardium. In contrast, there was only minimal uptake in the infarct of the blocked rats, comparable to the uptake in the remote noninfarcted myocardium (PET image–derived ratio of infarct uptake to remote uptake: 6 ± 2). Immunofluorescence staining confirmed the presence of FAP-positive myofibroblasts in the injured myocardium. Morphometric analysis of the whole-heart sections demonstrated 3- and 8-fold higher FAP-positive fibroblast density in the border zone than in the infarct center and remote area, respectively. Conclusion: ⁶⁸Ga-FAPI-04 represents a promising radiotracer for in vivo imaging of post-MI fibroblast activation. Noninvasive imaging of activated fibroblasts may have significant diagnostic and prognostic value, which could aid clinical management of patients after MI.

心力衰竭仍然是心肌梗塞（MI）后晚期发病率和死亡率的主要来源。受损心肌中颞成骨区存在活化的成纤维细胞，预示着心肌梗死后心脏重塑的质量。因此，监测活化的成纤维细胞对于研究MI后的心脏重塑非常重要。成纤维细胞活化蛋白（FAP）的表达在活化的成纤维细胞中被上调。这项研究调查了用新型⁶⁸ Ga标记的FAP抑制剂（⁶⁸ Ga-FAPI-04）对活化的成纤维细胞进行成像的可行性，以在MI的临床前模型中对成纤维细胞活化进行PET成像。方法：用MI和假手术大鼠进行^68次扫描Ga-FAPI-04 PET / CT（MI后1、3、6、14、23和30 d）和¹⁸ F-FDG（MI后3 d）。冠状动脉结扎后7 d对MI大鼠进行动态⁶⁸ Ga-FAPI-04 PET和阻断研究。体内扫描后，对动物实施安乐死，并收获其心脏进行离体分析。准备了冷冻切片用于放射自显影，苏木精和曙红（H＆E）以及免疫荧光染色。结果： 受伤的心肌中⁶⁸ Ga-FAPI-04吸收在冠状动脉结扎后第6天达到峰值。通过减少¹⁸ F-FDG摄取并通过PET / MR和H＆E染色证实，示踪剂在MI区域大量积累。放射自显影和H＆E横截面染色显示⁶⁸Ga-FAPI-04主要聚集在梗塞心肌的边界区域。相反，阻塞大鼠的梗塞只有极少的摄取，与远处非梗塞心肌的摄取相当（PET图像得出的梗塞摄取与远端摄取之比：6±2）。免疫荧光染色证实在受损的心肌中存在FAP阳性的成肌纤维细胞。全心切片的形态计量学分析表明，边界区的FAP阳性成纤维细胞密度分别比梗死中心和偏远地区高3到8倍。结论： ⁶⁸Ga-FAPI-04代表有希望的放射性示踪剂，用于MI后成纤维细胞活化的体内成像。活化的成纤维细胞的非侵入性成像可能具有重要的诊断和预后价值，这可能有助于MI后患者的临床管理。