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.

Prognostic value of 18F-FDG PET/CT in patients with relapsed multiple myeloma.

This study aimed to assess the prognostic value of 18F-fluorodeoxyglucose positron emission tomography/computer tomography (18F-FDG PET/CT) in patients with relapsed multiple myeloma (MM). Fifty-one consecutive patients with relapsed MM were enrolled in this retrospective study. 18F-FDG parameters based on the Italian Myeloma Criteria for PET Use (IMPeTUs) and clinical data were analyzed for overall survival (OS) and progression-free survival (PFS). The Cox proportional risk model was used for univariate and multivariate analysis, and Kaplan-Meier survival curves were used for survival analysis. The median length of follow-up was 20 months (IQR, 5-29 months), the median PFS for the entire cohort was 8 months (IQR, 3-17 months) and the median OS was 21 months (IQR, 8-49 months). Multivariate survival analysis demonstrated that the Deauville score of BM > 3 [HR 2.900, 95% CI (1.011, 8.319), P = 0.048] and the presence of EMD [HR 3.134, 95% CI (1.245, 7.891), P = 0.015] were independent predictors of poor PFS. The presence of EMD [HR 12.777, 95% CI (1.825, 89.461), P = 0.010] and the reduced platelets count [HR 7.948, 95% CI (1.236, 51.099), P = 0.029] were adversely associated with OS. 18F-FDG PET/CT parameters based on IMPeTUs have prognostic significance in patients with relapsed MM.

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.

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.

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.

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.

Imaging of cardiac fibroblast activation in patients with chronic thromboembolic pulmonary hypertension.

PURPOSE: The aim of this study was to explore the association of cardiac fibroblast activation with clinical parameters and cardiovascular magnetic resonance (CMR) imaging parameters in patients with chronic thromboembolic pulmonary hypertension (CTEPH). METHODS: Thirteen CTEPH patients were prospectively enrolled. All of the patients underwent cardiac 68Gallium-labelled fibroblast activation protein inhibitor (68 Ga-FAPI-04)-positron emission tomography/computed tomography (PET/CT), right heart catheterisation, and echocardiography, and 11 of them additionally underwent CMR. Thirteen control subjects were selected to establish the normal range of cardiac 68 Ga-FAPI-04 uptake. Cardiac 68 Ga-FAPI-04 uptake higher than that in the blood pool was defined as abnormal. The global and segmental maximum standardised uptake values (SUVmax) of the right ventricle (RV) were measured and further expressed as target-to-background ratio (TBRRV) with left ventricular lateral wall activity as background. Late gadolinium enhancement (LGE) was visually evaluated, and native-T1 times, enhanced-T1 times, and extracellular volume (ECV) were quantitatively measured. RESULTS: Ten CTEPH patients (77%) had abnormal 68 Ga-FAPI-04 uptake in RV, mainly located in the free wall, which was significantly higher than that in controls (TBRRV: 2.4 ± 0.9 vs 1.0 ± 0.1, P < 0.001). The TBRRV correlated positively with the thickness of RV wall (r = 0.815, P = 0.001) and inversely with RV fraction area change (RVFAC) (r = - 0.804, P = 0.001) and tricuspid annular plane systolic excursion (TAPSE) (r = - 0.678, P = 0.011). No correlation was found between 68 Ga-FAPI-04 activity and CMR imaging parameters. CONCLUSION: Fibroblast activation in CTEPH, measured by 68 Ga-FAPI-04 imaging, is mainly localised in the RV free wall. Enhanced fibroblast activation reflects the thickening of the RV wall and decreased RV contractile function.

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.

Prognostic value of cardiac inflammation in ST-segment elevation myocardial infarction: A 18F-fluorodeoxyglucose PET/CT study.

BACKGROUND: 18F-fluorodeoxyglucose (FDG) imaging is used to detect cardiac inflammation and predict functional outcome in acute myocardial infarction (MI). However, data on the correlation of post-MI acute cardiac inflammation evaluated by 18F-FDG imaging and major adverse cardiac events (MACE) are limited. Therefore, we sought to explore the prognostic value of cardiac 18F-FDG imaging in patients with acute ST-segment elevation MI (STEMI). METHODS: Thirty-six patients with STEMI underwent 18F-FDG positron emission tomography/computed tomography (PET/CT) 5 days after primary percutaneous coronary intervention. 18F-FDG activity in infarcted and remote regions, as well as peri-coronary adipose tissue (PCAT), were measured and expressed as the maximum standardized uptake value (SUVmax). Patients were followed to determine the occurrence of MACE. RESULTS: The infarcted myocardium had a higher 18F-FDG intensity than the remote area. Moreover, the PCAT of culprit coronary arteries showed a higher 18F-FDG uptake than that of non-culprit arteries. Multivariate Cox regression analysis showed that increased SUVmax of PCAT [HR 5.198; 95% CI (1.058, 25.537), P = .042] was independently associated with a higher risk of MACE. CONCLUSIONS: Enhanced PCAT activity after acute MI is related to the occurrence of MACE, and 18F-FDG PET/CT plays a promising role in providing prognostic information in patients with STEMI.

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.

Incremental value of epicardial fat volume to coronary artery calcium score and traditional risk factors for predicting myocardial ischemia in patients with suspected coronary artery disease.

BACKGROUND: Epicardial fat volume (EFV) has been reported to be associated with coronary artery disease (CAD). CAD is the leading cause of myocardial ischemia and myocardial ischemia is closely related to major adverse cardiovascular events. We hypothesized that EFV could provide incremental value to traditional risk factors and coronary artery calcium score (CACS) in predicting myocardial ischemia in Chinese patients with suspected CAD. METHODS: We retrospectively studied 204 Chinese patients with suspected CAD who underwent single-photon emission computerized tomography-myocardial perfusion imaging (SPECT-MPI) combined with computed tomography (CT). Pericardial contours were manually defined, and EFV was automatically calculated. A reversible perfusion defect with summed difference score (SDS) ≥ 2 was defined as myocardial ischemia. RESULTS: The myocardial ischemia group had higher EFV than normal MPI group (137.80 ± 34.95cm3 vs. 106.63 ± 29.10 cm3, P < .001). In multivariable logistic regression analysis, high EFV was significantly associated with myocardial ischemia [odds ratio (OR): 8.30, 95% CI: 3.72-18.49, P < .001]. Addition of EFV to CACS and traditional risk factors could predict myocardial ischemia more effectively, with larger AUC .82 (P < .001), positive net reclassification index .14 (P = .04) and integrated discrimination improvement .14 (P < .001). The bootstrap resampling method (times = 500) was used to internally validation and calculate the 95% confidence interval (CI) of the AUC (95% CI .75-.87). The calibration curve for the probability of myocardial ischemia demonstrated good agreement between prediction and observation. CONCLUSIONS: In Chinese patients with suspected CAD, EFV was significantly associated with myocardial ischemia, and improved prediction of myocardial ischemia above traditional risk factors and CACS.

Clinical Features and Outcomes of Pulmonary Artery Sarcoma.

OBJECTIVES: A retrospective cohort study was designed to describe the clinical features and outcomes of pulmonary artery sarcoma (PAS). METHODS: Twenty-two (22) consecutive patients diagnosed with PAS by pathological examination were enrolled and followed up until they died or until January 2020. The medical records were retrospectively reviewed to evaluate the clinical characteristics, image findings, and outcomes. RESULTS: 1) Twenty-one (21, 95.5%) patients were firstly misdiagnosed. Dyspnoea was the most common presenting symptom (19 of 22, 86.4%). 2) Filling defects in the right pulmonary artery were seen in 17 patients (77.3%) with computed tomography pulmonary angiography or magnetic resonance pulmonary angiography. Among those patients, 14 underwent positron emission tomography-computed tomography detection and 13 (92.9%) were found to have increased uptake value in the pulmonary artery. 3) The median survival (from diagnosis to death or January 2020) of the total series was 11.6 months (range, 0.7-68.5 months). The estimated cumulative survival rates at 1, 2, and 3 years were 52.6%, 32.8%, and 19.7%, respectively. Patients who received surgery and/or chemo-radiotherapy treatment had a better survival rate compared with patients without treatment (the estimated cumulative survival rates at 1, 2, and 3 years were 60.3%, 39.1%, and 29.3%, respectively, vs 33.3%, 16.6%, and 0, accordingly) and better survival time (median survival 17.02 vs 3.16 months, respectively) (p=0.025). CONCLUSIONS: Pulmonary artery sarcoma is easily misdiagnosed, as the symptoms and routine image detection are nonspecific. Positron emission tomography-computed tomography may be helpful in diagnosis. Surgery and/or chemo-radiotherapy offer a chance for better outcomes.

Myocardial Glucose Metabolism Is Increased in Newly Diagnosed Lung Adenocarcinoma.

BACKGROUND: Cardiac metabolism alterations may be involved in abnormalities of cancer patients' cardiovascular system. This study aimed to explore whether left ventricular myocardial glucose metabolism is altered and its related factors in newly diagnosed patients with lung adenocarcinoma (LAD) who underwent fluorine-18 fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT). METHODS: From our 18F-FDG PET/CT imaging database, 171 patients with newly diagnosed LAD and 43 nononcologic subjects with matched age and sex were retrospectively analyzed. The included patients underwent conventional 18F-FDG PET/CT imaging with a >12-h fasting before 18F-FDG administration. The standardized uptake values (SUVs) of the left ventricular (LV) myocardium, arterial wall, epicardial adipose tissue (EAT), spleen, and bone marrow were separately measured. Laboratory parameters and echocardiographic results were collected as well. LAD patients were divided into 2 groups based on the 95th percentile of LV maximal SUV (SUVmax) obtained from the 43 nononcologic subjects. Univariate analysis and multiple logistic regression analysis were used to identify significant factors. RESULTS: Higher LV SUVmax was found (3.8 [2.4, 7.7] vs. 3.0 [2.0, 5.4], p = 0.052) in LAD than that in nononcologic patients, whereas no significant differences of 18F-FDG uptake were found in the arterial wall, EAT, spleen, or bone marrow between LAD patients and controls. The maximum diameter (Dmax) of the LAD lesion, SUVmax of spleen, and SUVmax of EAT were related to LV SUVmax in LAD. CONCLUSIONS: Myocardial glucose metabolism is increased in patients with newly diagnosed LAD. Dmax of LAD lesion, spleen activity, and EAT activity contribute to the increased LV activity in LAD.

A cell-based fluorescent assay for FAP inhibitor discovery.

To facilitate the discovery of FAP inhibitors, a convenient cell-based fluorescent assay was developed by using a commonly available U87MG cell line and a FAP-specific substrate Suc-Gly-Pro-AMC. The assay enabled the fast determination of multiple IC50s by simply incubating a solution of phosphate-buffered saline in a 96-well plate within 30 min. The substrate specificity, cross-reaction and other related conditions were systematically optimized. This method was successfully applied to determine the IC50s of seven known inhibitors. The results are in consistence with the trend reported, which indicating that this practical assay is a valuable method to accelerate the discovery of FAP inhibitor.

Factors relevant to atrial 18F-fluorodeoxyglucose uptake in atrial fibrillation.

BACKGROUND: This retrospective study was designed to explore the factors relevant to increased atrial 18F-fluorodeoxyglucose (FDG) uptake in patients with atrial fibrillation (AF) who had undergone routine whole-body positron emission tomography/computed tomography (PET/CT) imaging. METHODS AND RESULTS: Forty-eight consecutive AF patients (32 persistent, 16 paroxysmal) were identified from our routine FDG PET/CT database. Twenty-two control subjects were selected to establish the normal range of FDG uptake (maximum standardized uptake value, SUVmax) in target tissues. A target-to-background ratio (TBR) was calculated to determine abnormal uptake in the atrium and atrial appendage (AA). Univariate comparisons and multivariate regression analyses were conducted to explore the factors associated with the increased FDG accumulation in the atrium and AA. Seventeen AF patients, all with persistent AF, had increased atrial FDG uptake. Most of them (14, or 82.4%) had increased uptake in the right atrium. Eleven AF patients, 9 with persistent AF, had increased uptake in the AA, and bilateral AAs were equally involved. Multivariate logistic regression analyses identified that female gender, persistent AF, and activity in epicardial adipose tissue (EAT) were independent factors predicting the increased activity of the atrium; also, SUVmax of the left ventricle was found for the AA. In addition, multivariate linear regression analyses showed that EAT activity was the only independent variable linearly correlated with the activity of the atrium and AA. CONCLUSIONS: Atrial uptake was present in persistent AF and localized mainly in the right atrium, whereas bilateral AAs could be equally involved. Multiple factors contributed to the increased activity in atrium; in particular, the EAT activity was independently correlated with the activity of the atrium and AA.

Functional significance of post-myocardial infarction inflammation evaluated by 18F-fluorodeoxyglucose imaging in swine model.

BACKGROUND: The aim of the study was to investigate the relationship between post-myocardial infarction (MI) inflammation and left ventricular (LV) remodeling in a swine model by 18F-fluorodeoxyglucose (FDG) imaging. METHODS: MI was induced in swine by balloon occlusion of the left anterior descending coronary artery. A series of FDG positron emission tomography (PET) images were taken within 2 weeks post-MI, employing a comprehensive strategy to suppress the physiological uptake of cardiomyocytes. Echocardiography was applied to evaluate LV volume, global and regional function. CD68+ macrophage and glucose transporters (GLUT-1, -3 and -4) were investigated by immunostaining. RESULTS: The physiological uptake of myocardium was adequately suppressed in 92.3% of PET scans verified by visual analysis, which was further confirmed by the minimal expression of myocardial GLUT-4. Higher FDG uptake was observed in the infarct than in the remote area and persisted within the observational period of 2 weeks. The FDG uptake of infarcted myocardium on day 1 post-MI was correlated with LV global remodeling, and the FDG uptake of infarcted myocardium on days 1 and 8 post-MI had a trend of correlating with regional remodeling of the infarct area. CONCLUSIONS: We here report a feasible swine model for investigating post-MI inflammation. FDG signal in the infarct area of swine persisted for a longer duration than has been reported in small animals. FDG activity in the infarct area could predict LV remodeling.

Correction to: Multiple cardiovascular involvements in Behçet's disease: unique utility of 18F-FDG PET/CT in diagnosis and follow-up.

Figure c of the original version of this article was not converted properly. Correct figure is presented here. The original article has been corrected.

Development and validation of the PET-CT score for diagnosis of malignant pleural effusion.

PURPOSE: Although some parameters of positron emission tomography with 18F-fluorodeoxyglucose (18F-FDG) and computed tomography (PET-CT) are somehow helpful in differentiating malignant pleural effusion (MPE) from benign effusions, no individual parameter offers sufficient evidence for its implementation in the clinical practice. The aim of this study was to establish the diagnostic accuracy of a scoring system based on PET-CT (the PET-CT score) in diagnosing MPE. METHODS: One prospective derivation cohort of patients with pleural effusions (84 malignant and 115 benign) was used to develop the PET-CT score for the differential diagnosis of malignant pleural effusion. The PET-CT score was then validated in another independent prospective cohort (n = 74). RESULTS: The PET-CT parameters developed for discriminating MPE included unilateral lung nodules and/or masses with increased 18F-FDG uptake (3 points); extrapulmonary malignancies (3 points); pleural thickening with increased 18F-FDG uptake (2 points); multiple nodules or masses (uni- or bilateral lungs) with increased 18F-FDG uptake (1 point); and increased pleural effusion 18F-FDG uptake (1 point). With a cut-off value of 4 points in the derivation cohort, the area under the curve, sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of the PET-CT score to diagnose MPE were 0.949 (95% CI: 0.908-0.975), 83.3% (73.6%-90.6%), 92.2% (85.7%-96.4%), 10.7 (5.6-20.1), and 0.2 (0.1-0.3), respectively. CONCLUSIONS: A simple-to-use PET-CT score that uses PET-CT parameters was developed and validated. The PET-CT score can help physicians to differentiate MPE from benign pleural effusions.

Relationship of myocardial hibernation, scar, and angiographic collateral flow in ischemic cardiomyopathy with coronary chronic total occlusion.

BACKGROUND: The relationship between myocardial viability and angiographic collateral flow is not fully elucidated in ischemic cardiomyopathy (ICM) with coronary artery chronic total occlusion (CTO). We aimed to clarify the relationship between myocardial hibernation, myocardial scar, and angiographic collateral flow in these patients. METHODS AND RESULTS: Seventy-one consecutive ICM patients with 122 CTOs and 652 dysfunctional segments within CTO territories were retrospectively analyzed. Myocardial hibernation (perfusion-metabolism mismatch) and the extent of 18F-fluorodeoxyglucose (FDG) abnormalities were assessed using 99mTc-sestamibi and 18F-FDG imaging. Myocardial scar was evaluated by late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) imaging. Collateral flow observed on coronary angiography was assessed using Rentrop classification. In these patients, neither the extent nor frequency of myocardial hibernation or scar was related to the status of collateral flow. Moreover, the matching rate in determining myocardial viability was poor between any 2 imaging indices. The extent of 18F-FDG abnormalities was linearly related to the extent of LGE rather than myocardial hibernation. Of note, nearly one-third (30.4%) of segments with transmural scar still had hibernating tissue. Hibernation and non-transmural scar had higher sensitivity (63.0% and 66.7%) than collateral flow (37.0%) in predicting global functional improvement. CONCLUSIONS: Angiographic collateral cannot accurately predict myocardial viability, and has lower sensitivity in prediction of functional improvement in CTO territories in ICM patients. Hence, assessment of myocardial viability with non-invasive imaging modalities is of importance. Moreover, due to the lack of correlation between myocardial hibernation and scar, these two indices are complementary but not interchangeable.