Molecular Imaging of Fibroblast Activation in Rabbit Atherosclerotic Plaques: a Preclinical PET/CT Study.

AIM: Atherosclerosis remains the pathological basis of myocardial infarction and ischemic stroke. Early and accurate identification of plauqes is crucial to improve clinical outcomes of atherosclerosis patients. Our study aims to evaluate the potential value of fibroblast activation protein inhibitor (FAPI)-04 PET/CT in identifying plaques via a preclinical rabbit model of atherosclerosis. METHODS: New Zealand white rabbits were fed high-fat diet (HFD), and randomly divided into the model group injured by the balloon, and the sham group only with incisions. Ultrasound was performed to detect plaques, and FAPI-avid was determined through Al18F-NOTA-FAPI-04 PET/CT. Mean standardized uptake values (SUVmean) in lesions were compared, and biodistribution of Al18F-NOTA-FAPI-04 and target-to-background ratios (TBRs) were calculated. Histological staining was performed to display arterial plaques, and autoradiography (ARG) was employed to measure the in vitro intensity of Al18F-NOTA-FAPI-04. At last, the correlation among FAP levels, plaque area, SUVmean values and fibrous cap thickness was assessed. RESULTS: The rabbit carotid and abdominal atherosclerosis model was established. Al18F-NOTA-FAPI-04 showed a higher uptake in carotid plaques (SUVmean 1.32 ± 0.11) and abdominal plaques (SUVmean 0.73 ± 0.13) compared to corresponding controls (SUVmean 1.07 ± 0.06; 0.46 ± 0.03) (P < 0.05). Biodistribution analysis of Al18F-NOTA-FAPI-04 revealed that the bigger plaques were delineated with higher TBRs. Pathological staining showed the formation of arterial plaques, and ARG staining exhibited a higher intensity of Al18F-NOTA-FAPI-04 in the bigger plaques. Lastly, plaque area was found to be positively correlated to FAP expression and SUVmean, while FAP expression was negatively correlated to fibrous cap thickness of plaques. CONCLUSIONS: We successfully achieve molecular imaging of fibroblast activation in atherosclerotic lesions of rabbits, suggesting Al18F-NOTA-FAPI-04 PET/CT may be a potentially valuable tool to identify plaques.

Early detection of anthracycline-induced cardiotoxicity using [68 Ga]Ga-FAPI-04 imaging.

PURPOSE: Anthracycline-induced cardiotoxicity (AIC), whose major manifestation is diffuse myocardial fibrosis, is an important clinical problem in cancer therapy. Therefore, early identification and treatment are clinically important. This study aims to explore the feasibility of using 68 Ga-labelled fibroblast activation protein (FAP) inhibitor ([68 Ga]Ga-FAPI) positron emission tomography/computed tomography (PET/CT) for the early identification of the fibrotic process and guidance of antifibrosis therapy in AIC. METHODS: An AIC rat model was induced by the intravascular administration of doxorubicin (DOX) once per week for 1, 2, 3 and 6 weeks (2.5 mg/kg/injection, groups 1-4), whereas intravascular saline was administered to control rats. Experimental and control groups (n = 4) underwent [68 Ga]Ga-FAPI PET/CT following disease induction. Groups 5 and 6 received DOX injections for 3 and 6 weeks, treated with angiotensin-converting enzyme (ACE) inhibitor starting at 3 weeks, treated with enalapril (20 mg/kg, gastric gavage) daily and underwent echocardiography and [68 Ga]Ga-FAPI PET/CT at 3 weeks after treatment. Rat hearts were subjected to haematoxylin and eosin staining, FAP immunohistochemistry, Sirius red staining and Masson's trichrome staining to investigate the pathological changes and deposition of collagen fibres. Rat blood was sampled weekly for the enzyme-linked immunosorbent assay of various markers of myocardial injury, such as plasma cardiac troponin I, B-type natriuretic peptide and angiotensin II. RESULTS: [68 Ga]Ga-FAPI-04 uptake by the heart was significantly higher in the cardiotoxicity group than in the control group at weeks 3 (SUVmax: 1.21 ± 0.23 vs 0.67 ± 0.01, P < 0.05) and 6 (SUVmax: 1.48 ± 0.28 vs 0.67 ± 0.08, P < 0.001), whereas left ventricle ejection fraction (LVEF) did not significantly differ between normal and AIC rats at week 3. FAP+ expression began to increase starting at week 3, before irreversible fibrotic changes were detected, until week 6. After 3 weeks of enalapril treatment, [68 Ga]Ga-FAPI-04 accumulation decreased in groups 5 and 6 (SUVmax decreased from 1.21 ± 0.23 to 0.77 ± 0.08 and 1.48 ± 0.28 to 1.09 ± 1.06, P < 0.05). Cardiac function was preserved (LVEF was 75.7% ± 7.38% in group 3 vs 74.5% ± 2.45% in group 5, P > 0.05) and improved (LVEF increased from 51.6% ± 9.03% in group 4 to 65.2% ± 4.27% in group 6, P < 0.05), and myocardial fibrosis attenuated (from 6.5% ± 1.2% in group 4 to 4.31% ± 0.37% in group 6, P < 0.01). CONCLUSION: [68 Ga]Ga-FAPI PET/CT can be used for the early detection of active myocardial fibrosis in AIC and the evaluation of the efficacy of therapeutic interventions. Early treatment guided by [68 Ga]Ga-FAPI PET/CT may reduce anthracycline-induced myocardial injury and improve heart function.

Development of a 18F-Labeled Bicyclic Peptide Targeting EphA2 for Molecular Imaging of PSMA-Negative Prostate Cancer.

Although PSMA PET/CT imaging has great potential for noninvasively detecting prostate cancer (PCa), limitations exist for patients with low PSMA expression, caused by androgen deprivation treatment or neuroendocrine differentiation. Analysis of The Cancer Genome Atlas Prostate Adenocarcinoma (TCGA-PRAD) data found that erythropoietin-producing hepatocellular receptor A2 (EphA2), a receptor overexpressed in most PCa could be a potential target for PSMA-negative PCa. A fluorescent ligand ETF and a radiolabeled ligand [18F]AlF-ETN derived from a EphA2-targeting bicyclic peptide were synthesized and investigated. ETF could selectively stain and visualize the EphA2-positive but PSMA-negative PC3 cells, in complementary to the PSMA-targeting probe. PET/CT imaging and biodistribution experiments demonstrated that [18F]AlF-ETN specifically accumulated in PC3 tumors with a high contrast (tumor-to-muscle ratio: 21.29 ± 6.55). In conclusion, we have demonstrated the potential for using EphA2 to detect PSMA-negative PCa and developed a radiolabeled ligand [18F]AlF-ETN to specifically image EphA2 expressing PCa with high contrast.

Fibroblast activation protein imaging in atrial fibrillation: a proof-of-concept study.

BACKGROUND: To evaluate the feasibility of using radiolabeled fibroblast activation protein inhibitor (FAPI) PET/CT imaging to assess activated fibroblasts in the atria of individuals with AF and to identify factors contributing to enhanced atrial activity. METHODS: We constructed left atrial appendage (LAA) pacing beagle dog AF models (n = 5) and conducted 18F-FAPI PET/CT imaging at baseline and eight weeks after pacing. Right atrial (RA) specimens were collected from these models. Additionally, 28 AF patients and ten age- and sex-matched healthy volunteers underwent 18F-FAPI PET/CT imaging. RESULTS: RA of AF beagles showed increased 18F-FAPI uptake. Among AF patients, 18 out of 28 (64.3%) exhibited enhanced atrial FAPI activity. No atrial 18F-FAPI uptake was observed in the sham beagle and healthy volunteers. In animal RA specimens, 18F-FAPI activity correlated positively with FAP mRNA (r = .98, P = .002) and protein (r = .82, P = .03) levels, as well as collagen I mRNA expression (r = .85, P = .02). B-type natriuretic peptide levels were associated with atrial 18F-FAPI activity (OR = 3.01, P = .046). CONCLUSION: This proof-of-concept study suggests that 18F-FAPI PET/CT imaging may be a feasible method for evaluating activated fibroblasts in the atria of AF patients.

99mTc-HFAPi imaging identifies early myocardial fibrosis in the hypertensive heart.

BACKGROUND: This study aimed to explore whether 99mTc-radiolabeled fibroblast activation protein inhibitor (99mTc-HFAPi) imaging can detect early myocardial fibrosis in the hypertensive heart. METHODS: In the experimental model, spontaneously hypertensive rats (SHRs) and age-matched Wistar Kyoto rats (WKYs) were randomly divided into three groups (8, 16, and 28 weeks). The animals underwent 99mTc-HFAPi imaging and echocardiography. Autoradiography and histological analyses were performed in the left ventricle. The mRNA and protein expression level of the fibroblast activation protein (FAP) and collagen I were measured using quantitative PCR and western blot. In the clinical investigation, a total of 106 patients with essential hypertension and 20 gender-matched healthy controls underwent 99mTc-HFAPi imaging and echocardiography. RESULTS: In-vivo and in-vitro autographic images demonstrated diffusely enhanced 99mTc-HFAPi uptake in the SHR heart starting at week 8, before irreversible collagen deposition. The mRNA and protein levels of FAP in SHRs began to increase from week 8, whereas changes in collagen I levels were not detected until week 28. In the clinical investigation, even in hypertensive patients with normal diastolic indicators, normal left ventricular geometry, and normal global longitudinal strain (GLS), the prevalence of increased 99mTc-HFAPi uptake reached 34, 41, and 20%, respectively, indicating that early fibrogenesis precedes structural and functional myocardial abnormalities. CONCLUSION: In hypertension, 99mTc-HFAPi imaging can detect early fibrotic process before myocardial functional and structural changes.

Functional significance of myocardial activity at 18F-FAPI PET/CT in hypertrophic cardiomyopathy identified by cardiac magnetic resonance feature-tracking strain analysis.

PURPOSE: This study aimed to evaluate the functional significance of 18F-labeled fibroblast activation protein inhibitor (18F-FAPI) activity in hypertrophic cardiomyopathy (HCM) by comparison with cardiac magnetic resonance feature-tracking (CMR-FT) strain analysis. METHODS: A total of 49 HCM patients were included in this study. Two independent control groups of healthy participants with a matched age and sex to the HCM patients were also enrolled. Left ventricular (LV) 18F-FAPI activity was analyzed for extent (FAPI%) and intensity (maximum target-to-background ratio, TBRmax). The CMR tissue characterization parameters of the LV included late gadolinium enhancement, native T1 value, and extracellular volume fraction. LV strain analysis was performed in radial, circumferential, and longitudinal peak strains (PS). RESULTS: Intense LV myocardial 18F-FAPI uptake was observed in HCM patients, whereas no obvious uptake was detected in healthy participants (median TBRmax, 9.1 vs. 1.2, p < 0.001). The strain parameters of HCM patients, compared with healthy participants, were significantly impaired (mean radial PS, 23.5 vs. 36.0, mean circumferential PS, -14.5 vs. -20.0, and mean longitudinal PS, -9.9 vs. -16.0, all p < 0.001). At segmental levels, there was a moderate correlation between 18F-FAPI activity and strain parameters. The number of positive 18F-FAPI uptake segments (n = 653) was higher than that of hypertrophic segments (n = 190) and positive CMR tissue characterization segments (n = 525) (all p < 0.001). In segments with negative CMR tissue characterization findings, the strain capacity of positive 18F-FAPI uptake segments was lower than that of negative 18F-FAPI uptake segments (median radial PS, 30.5 vs. 36.1, p = 0.026 and median circumferential PS, -18.4 vs. -19.7, p = 0.041). CONCLUSION: 18F-FAPI imaging can partially reflect the potential strain reduction in HCM patients. 18F-FAPI imaging detects more involved myocardium than CMR tissue characterization techniques, and the additionally identified myocardium has impaired strain capacity.

SGLT2i alleviates epicardial adipose tissue inflammation by modulating ketone body-glyceraldehyde-3-phosphate dehydrogenase malonylation pathway.

AIMS: Inflammation in the epicardial adipose tissue (EAT) is a contributor to atrial fibrillation. Studies have reported that sodium glucose co-transporter 2 inhibitor (SGLT2i) can alleviate EAT inflammation. However, the mechanism remains elusive. This study aims to investigate the molecular mechanism of SGLT2i in reducing EAT inflammation and to explore the effects of SGLT2i on atrial fibrosis in atrial fibrillation. METHODS: Sprague-Dawley rats were injected with angiotensin II to induce atrial fibrillation and randomly assigned to receive SGLT2i ( n  = 6) or vehicle ( n  = 6). Macrophages (RAW264.7) were treated with ketone bodies; ACC1 knockdown/overexpression and malonyl-CoA overexpression were performed in vitro . The levels of inflammatory cytokines, ACC1, and malonyl-CoA were examined by ELISA. GAPDH malonylation was measured by co-immunoprecipitation. RESULTS: In atrial fibrillation rats, SGLT2i increased the ketone body levels and decreased the expression of ACC1 and alleviated EAT inflammation and atrial fibrosis. In RAW264.7 cells, ketone bodies decreased the levels of ACC1, malonyl-CoA, and GAPDH malonylation, accompanied by reduced inflammatory cytokines. ACC1 knockdown decreased the expression of malonyl-CoA and GAPDH malonylation and alleviated lipopolysaccharide (LPS)-induced macrophage inflammation; these effects were inhibited by malonyl-CoA overexpression. Furthermore, the protective effects of ketone bodies on macrophage inflammation were abrogated by ACC1 overexpression. CONCLUSION: SGLT2i alleviates EAT inflammation by reducing GAPDH malonylation via downregulating the expression of ACC1 through increasing ketone bodies, thus attenuating atrial fibrosis.

Delayed contrast-enhanced magnetic resonance imaging enables detection of pulmonary artery lesions in Takayasu's arteritis.

Background: Delayed contrast-enhanced magnetic resonance imaging (DE-MRI) is a useful technique to identify arterial wall inflammation. The aim of this study was to explore the value of DE-MRI in the evaluation of pulmonary artery (PA) lesions in Takayasu's arteritis (TAK) compared with 18F-fuorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT). Methods: Patients with TAK were recruited for this prospective, observational study. Imaging and clinical assessments were performed concurrently. Only thoracic arteries were evaluated, and they were divided into 18 segments per person. All arterial lesions were evaluated using both PET/CT and DE-MRI. Correlations between both methods were assessed in the PA and thoracic aorta. A receiver operating characteristic (ROC) curve was used to analyze the value of imaging features in detecting disease activity based on National Institutes of Health (NIH) criteria. Results: A total of 24 patients contributed 432 arterial segments. Using PET/CT, correlations between arterial wall DE, thickening, and edema in the PA were 84.52%, 67.92%, and 58.33%, respectively, with Cohen's kappa =0.69, 0.30, and 0.13, respectively; for the thoracic aorta, the values were 86.38%, 80.00%, and 75.92%, respectively, with Cohen's kappa =0.71, 0.52, and 0.372, respectively. There was a significant difference in the incidence of wall DE between the PA and thoracic aorta in patients with clinically active TAK (χ2=6.85, P=0.009). DE-MRI presented a higher area under the curve [area under the curve (AUC); 0.729, P=0.047] than wall thickening and edema in the detection of TAK activity. The wall DE combined with erythrocyte sedimentation rate (ESR) showed improved efficiency (AUC: 0.858, P=0.003). Conclusions: DE-MRI displays appreciable correlations with PET/CT findings and allows for the detection of PA inflammation in patients with TAK; it shows higher values in the thoracic aorta than in the PA. The combination of wall DE and ESR can improve the efficiency of assessing disease status.

Value of 99m Tc-MIBI SPECT/CT in the localization of recurrent lesions in patients with suspected recurrent parathyroid carcinoma.

PURPOSE: Accurate preoperative localization of tumor-bearing lesions is crucial for the successful surgical management of suspected recurrent parathyroid carcinoma. The purpose of this study was to evaluate the diagnostic value of 99m-technetium-labeled methoxyisobutylisonitrile ( 99m Tc-MIBI) single-photon emission computed tomography/computed tomography (SPECT/CT) and cervical ultrasound, individually and in combination, for preoperative localization of recurrent/metastatic lesions. We also analyzed the value of 99m Tc-MIBI SPECT/CT in detecting ectopic lesions in patients with suspected recurrent parathyroid carcinoma. METHODS: Twenty-nine patients with suspected recurrent parathyroid carcinoma were included in this retrospective cohort study. Patients underwent preoperative 99m Tc-MIBI SPECT/CT and cervical ultrasound. The reference standard was postsurgical histopathology. The sensitivity, specificity, positive predictive value (PPV), negative predictive value, and accuracy of the two diagnostic modalities alone and in combination were analyzed. RESULTS: Of the 29 patients, histopathological results revealed 48 metastases/recurrent lesions in 26 patients. The diagnostic value of 99m Tc-MIBI SPECT/CT, cervical ultrasound, and the two modalities in combination were compared for the 27 patients who underwent new cervical surgery. Patient-level analysis of the combined use of 99m Tc-MIBI SPECT/CT and cervical ultrasound had the highest sensitivity (100.00%) and accuracy (96.30%). At the lesion level, 99m Tc-MIBI SPECT/CT had the highest specificity and PPV, at 100.00% respectively, whereas the combined use of 99m Tc-MIBI SPECT/CT and cervical ultrasound had the highest sensitivity, at 97.62%. Moreover, 99m Tc-MIBI SPECT/CT detected six ectopic lesions, and five of them showed increased 99m Tc-MIBI uptake. CONCLUSIONS: The combined use of 99m Tc-MIBI SPECT/CT and cervical ultrasound is the most efficient strategy in the diagnosis of parathyroid carcinoma relapse, whereas 99m Tc-MIBI SPECT/CT is the preferred method for localizing and analyzing cervical and extra-cervical lesions before the new surgery.

Myocardial Activity at 18F-FAPI PET/CT and Risk for Sudden Cardiac Death in Hypertrophic Cardiomyopathy.

Background Myocardial fibrosis contributes to adverse cardiovascular events in hypertrophic cardiomyopathy (HCM). Purpose To explore the characteristics of cardiac fibroblast activation protein inhibitor (FAPI) PET/CT imaging and its relationship with the risk of sudden cardiac death (SCD) in HCM. Materials and Methods In this prospective study from July 2021 to January 2022, participants with HCM and healthy control participants underwent cardiac fluorine 18 (18F)-labeled FAPI PET/CT imaging. Myocardial FAPI activity was quantified as intensity (target-to-background uptake ratio), extent (the percent of FAPI-avid myocardium of the left ventricle [LV]), and amount (the percent of FAPI-avid myocardium of LV × target-to-background ratio). Regional wall thickness was analyzed at cardiac MRI. The 5-year SCD risk score was calculated from the 2014 European Society of Cardiology guidelines. Univariable and multivariable linear regression analyses were used to identify factors related to the FAPI amount. The correlation between FAPI amount and 5-year SCD risk was explored. Results Fifty study participants with HCM (mean age, 43 years ± 13 [SD]; 32 men) and 22 healthy control participants (mean age, 45 years ± 17; 14 men) were included. All participants with HCM had intense and inhomogeneous cardiac FAPI activity in the LV myocardium that was higher than that in healthy control participants (median target-to-background ratio, 8.8 vs 2.1, respectively; P < .001). In HCM, more segments with FAPI activity were detected than the number of hypertrophic segments (median, 14 vs five, respectively; P < .001); 84% of nonhypertrophic segments showed FAPI activity. Log-transformed FAPI amount had a positive relationship with log-transformed N-terminal probrain natriuretic peptide, high-sensitive troponin I, and left atrial diameter and a negative relationship with LV ejection fraction z-score. Degree of FAPI activity positively correlated with the 5-year SCD risk score (r = 0.32; P = .03). Conclusion Fibroblast activation protein inhibitor (FAPI) PET/CT imaging indicated intense and heterogeneous activity in hypertrophic cardiomyopathy, and FAPI uptake was associated with 5-year risk of sudden cardiac death. © RSNA, 2022 Online supplemental material is available for this article.

Pulmonary artery imaging with 68 Ga-FAPI-04 in patients with chronic thromboembolic pulmonary hypertension.

BACKGROUND: The feasibility and significance of imaging pulmonary artery (PA) remodeling with 68 Ga-fibroblast activating protein inhibitor (FAPI) in patients with chronic thromboembolic pulmonary hypertension (CTEPH) have not yet been addressed. METHODS: 68 Ga-FAPI-04 uptake in the PA and ascending artery was evaluated in 13 patients with CTEPH and 13 matched non-CTEPH controls. The correlations of PA 68 Ga-FAPI-04 uptake and remodeling parameters derived from right heart catheterization (RHC) were analyzed. RESULTS: Of the 13 patients with CTEPH, nine (69%) showed visually enhanced 68 Ga-FAPI-04 uptake, whereas none of the control subjects had increased 68 Ga-FAPI-04 uptake in the PA. The prevalence of enhanced uptake in the main, lobar, and segmental PAs was 45% (17/38), 33% (16/48), and 28% (44/159), respectively. 68 Ga-FAPI-04 activity in the PA was positively correlated with pulmonary arterial diastolic pressure (r = 0.571, P = 0.041). CONCLUSION: 68 Ga-FAPI-04 has the potential for imaging fibroblast activation in the PA wall, and 68 Ga-FAPI-04 activity in PA is positively correlated with pulmonary arterial diastolic pressure.

18F-FDG PET/CT of Primary Extraskeletal Ewing Sarcoma of the Prostate.

ABSTRACT: Prostate Ewing sarcoma is rare. We report the 18F-FDG PET/CT finding of a 16-year-old adolescent boy who presented with dysuria and was confirmed to be extraskeletal Ewing sarcoma of the prostate by histopathologic findings.

Increased 18F-ALF-NOTA-FAPI and 18F-FDG Uptake in Renal Angiomyolipoma.

ABSTRACT: Angiomyolipoma is a common benign tumor in the kidney. Previous publication reported that renal angiomyolipoma had very low to low uptake of 18F-FDG. We report a case of pathologically proven angiomyolipoma in the left kidney with intense 18F-FDG and 18F-ALF-NOTA-FAPI uptake.

Association of atrial 18F-fluorodeoxyglucose uptake and prior ischemic stroke in non-atrial fibrillation patients.

BACKGROUND: Atrial cardiomyopathy has gained increasing attention in the field of ischemic stroke due to its prothrombotic substrate. Timely identification of high-risk individuals without atrial fibrillation (AF) is essential in secondary prevention. We sought to explore the feasibility of atrial 18F-fluorodeoxyglucose (FDG) imaging in detecting diseased atrial substrate and in identifying ischemic stroke in a non-AF population. METHODS: 1444 non-AF inpatients were initially identified. Among them, 196 patients had enhanced atrial FDG uptake, while 392 patients without atrial activity were selected as controls. Atrial activity, the history of ischemic stroke, and atrial cardiomyopathy were analyzed. RESULTS: Patients with atrial cardiomyopathy had a higher prevalence of enhanced atrial activity (47.1% vs 26.0%, P < .001), and patients with increased atrial activity had a higher prevalence of a prior history of ischemic stroke (12.2% vs 3.3%, P < .001). Multivariate regression analysis demonstrated that atrial activity was independently related to ischemic stroke after adjustment for risk factors (OR 4.02, 95% CI 1.97-8.19, P < .001) and atrial cardiomyopathy (OR 3.63, 95% CI 1.51-8.74, P = .004). CONCLUSIONS: This study identified an association between atrial FDG activity and a history of ischemic stroke and atrial cardiomyopathy in non-AF individuals. Further longitudinal study is warranted to demonstrate their causal relationship.

Fibroblast activation protein imaging in reperfused ST-elevation myocardial infarction: comparison with cardiac magnetic resonance imaging.

PURPOSE: The aim of this study was to explore the correlation of 18F-labeled fibroblast activation protein inhibitor (FAPI) and cardiovascular magnetic resonance (CMR) parameters in ST-elevation myocardial infarction (STEMI) patients with successful primary percutaneous coronary intervention (PPCI) and to investigate the value of FAPI imaging in predicting cardiac functional recovery, as well as the correlation between FAPI activity and circulating fibroblast activation protein (FAP) and inflammatory biomarkers. METHODS: Fourteen first-time STEMI patients (11 men, mean age: 62 ± 11 years) after PPCI and 14 gender-matched healthy volunteers (10 men, mean age: 50 ± 14 years) who had completed FAPI imaging and blood sample collection were prospectively recruited. All patients underwent baseline FAPI imaging (6 ± 2 days post-MI) and CMR (8 ± 2 days post-MI). Ten patients had follow-up CMR (84 ± 4 days post-MI). Myocardial FAPI activity was analyzed for extent (the percentage of FAPI uptake volume over the left ventricular volume, FAPI%), intensity (target-to-background uptake ratio, TBRmax), and amount (FAPI% × TBRmax). Late gadolinium enhancement (LGE), T2-weighted imaging (T2WI), extracellular volume (ECV), microvascular obstruction (MVO), and cardiac function from CMR imaging were analyzed. Blood samples obtained on the day of FAPI imaging were used to assess circulating FAP, TGF-ß1, TNF-α, IL-6, and hsCRP in STEMI patients and controls. RESULTS: Localized but inhomogeneous FAPI uptake was observed in STEMI patients, which was larger than the edematous and infarcted myocardium, whereas no uptake was detected in controls. The MVO area showed lower FAPI uptake compared with the surrounding myocardium. FAPI activity was associated with the myocardial injury biomarkers T2WI, LGE, and ECV at both per-patient and per-segment levels (all p < 0.05), but was not associated with circulating FAP, TGF-ß1, TNF-α, IL-6, or hsCRP. Among the CMR parameters, T2WI had the greatest correlation coefficient with both FAPI% and FAPI% × TBRmax. Baseline TBRmax was inversely correlated with the follow-up left ventricular ejection fraction (LVEF) (r = - 0.73, p = 0.02). CONCLUSION: FAPI imaging detects more involved myocardium than CMR in reperfused STEMI, and is associated with myocardial damage and follow-up LVEF.