Diagnostic efficacy of [68Ga]Ga-DOTA-GPFAPI-04 in patients with solid tumors in a head-to-head comparison with [18F]F-FDG: results from a prospective clinical study.

PURPOSE: To identify the biodistribution and diagnostic performance of a novel fibroblast activation protein (FAP) targeted positron emission tomography (PET) tracer, [68Ga]Ga-DOTA-GPFAPI-04, in patients with solid tumors in a head-to-head comparison with [18F]F-FDG. METHODS: Twenty-six patients histologically proven with cancers of nasopharyngeal (n = 5), esophagus (n = 5), gastro-esophagus (n = 1), stomach (n = 7), liver (n = 3), and colorectum (n = 5) were recruited for [68Ga]Ga-DOTA-GPFAPI-04 and [18F]F-FDG PET/CT scans on consecutive days. The primary endpoint was the diagnostic efficacy, with the histological diagnosis and the follow-up results selected as the gold standard. The secondary endpoint was the background uptake pattern. Two experienced nuclear medicine physicians who were blinded to the gold standard results while having essential awareness of the clinical context reviewed the images and labeled lesions by consensus for subsequent software-assisted lesion segmentation. Additionally, background organs were automatically segmented, assisted by artificial intelligence. Volume, mean, and maximum standard uptake values (SUVmean and SUVmax) of all segmentations were recorded. P < 0.05 was deemed as statistically significant. RESULTS: Significant glandular uptake of [68Ga]Ga-DOTA-GPFAPI-04 was detected in the thyroid, pancreas, and submandibular glands, while moderate uptake was observed in the parotid glands. The myocardium and myometrium exhibited 2-3 times higher uptake of the radiotracer than that of the background levels in blood and liver. A total of 349 targeted lesions, consisting of 324 malignancies and 25 benign lesions, were segmented. [68Ga]Ga-DOTA-GPFAPI-04 is more sensitive than [18F]F-FDG, especially for abdominopelvic dissemination (1.000 vs. 0.475, P < 0.001). Interestingly, [18F]F-FDG demonstrated higher sensitivity for lung metastasis compared to [68Ga]Ga-DOTA-GPFAPI-04 (0.845 vs. 0.682, P = 0.003). The high glandular uptake made it difficult to delineate lesions in close proximity and masked two metastatic lesions in these organs. CONCLUSION: Despite prominent glandular uptake, [68Ga]Ga-DOTA-GPFAPI-04 demonstrates favorable diagnostic performance. It is a promising probe scaffold for further development of FAP-targeted tumor theranostic agents.

Kinetic modeling and parametric imaging of 18 F-PSMA-11: An evaluation based on total-body dynamic positron emission tomography scans.

BACKGROUND: The prostate-specific membrane antigen (PSMA) targeted positron-emitting tomography (PET) tracers are increasingly used in clinical practice, with novel tracers constantly being developed. Recently, 18 F-PSMA-11 has been gaining growing interest for several merits; however, direct in vivo visualization of its kinetic features in humans remains lacking. PURPOSE: To visualize the kinetic features of 18 F-PSMA-11 in healthy subjects and patients with prostate cancer derived from the total-body dynamic PET scans. METHODS: A total of 8 healthy volunteers (7 males; 1 female) and 3 patients with prostate cancer underwent total-body PET/CT imaging at 1 and 2 h post injection (p.i.) of 18 F-PSMA-11, of which 7 healthy subjects and 3 patients underwent total-body dynamic PET scans lasting 30 min. Reversible two-tissue compartments (2TC) and Patlak models were fitted based on the voxel-based time activity curves (TACs), with the parametric images generated subsequently. Additionally, semi-automated segmentation of multiple organs was performed in the dynamic images to measure the SUVmean at different time points and in the parametric images to estimate the mean value of the kinetic parameters of these organs. RESULTS: 18 F-PSMA-11 showed quick accumulation within prostate cancer, as early as 45 s after tracer injection. It was rapidly cleared from blood circulation and predominantly excreted through the urinary system. High and rapid radiotracer accumulation was observed in the liver, spleen, lacrimal glands, and salivary glands, whereas gradual accumulation was observed in the skeleton. Prostate cancer tissue is visualized in all parametric images, and best seen in DV and Patlak Ki images. Patlak Ki showed a good correlation with 2TC Ki values (r = 0.858, p < 0.05) but less noise than 2TC images. A scanning time point of 30-35 min p.i. was then suggested for satisfactory tumor to background ratio. CONCLUSION: Prostate cancer tissue is visible in most parametric images, and is better shown by Patlak Ki and 2TC DV images. Patlak Ki is consistent with, and thus is preferred over, 2TC Ki images for substantially quicker calculation. Based on the dynamic imaging analysis, a shorter uptake time (30-35 min) might be preferred for a better balance of tumor to background ratio.

Ringlike late gadolinium enhancement provides incremental prognostic value in non-classical arrhythmogenic cardiomyopathy.

BACKGROUND: The 2019 arrhythmogenic right ventricular cardiomyopathy (ARVC) risk model has proved insufficient in the capability of predicting ventricular arrhythmia (VA) risk in non-classical arrhythmogenic cardiomyopathy (ACM). Furthermore, the prognostic value of ringlike late gadolinium enhancement (LGE) of the left ventricle in non-classical ACM remains unknown. We aimed to assess the incremental value of ringlike LGE over the 2019 ARVC risk model in predicting sustained VA in patients with non-classical ACM. METHODS: In this retrospective study, consecutive patients with non-classical ACM who underwent CMR from January 2011 to January 2022 were included. The pattern of LGE was categorized as no, non-ringlike, and ringlike LGE. The primary outcome was defined as the occurrence of sustained VA. Univariable and multivariable Cox regression analysis was used to evaluate the impact of LGE patterns on sustained VA and area under curve (AUC) was calculated for the incremental value of ringlike LGE. RESULTS: A total of 73 patients were collected in the final cohort (mean age, 39.3 ± 14.4 years, 51 male), of whom 10 (13.7%) had no LGE, 33 (45.2%) had non-ringlike LGE, and 30 (41.1%) had ringlike LGE. There was no statistically significant difference in the 5-year risk score among the three groups (P = 0.190). During a median follow-up of 34 (13-56) months, 34 (46.6%) patients experienced sustained VA, including 1 (10.0%), 13 (39.4%) and 20 (66.7%) of patients with no, non-ringlike and ringlike LGE, respectively. After multivariable adjustment, ringlike LGE remained independently associated with the presence of sustained VA (adjusted hazard ratio: 6.91, 95% confidence intervals: 1.89-54.60; P = 0.036). Adding ringlike LGE to the 2019 ARVC risk model showed significantly incremental prognostic value for sustained VA (AUC: 0.80 vs. 0.67; P = 0.024). CONCLUSION: Ringlike LGE provides independent and incremental prognostic value over the 2019 ARVC risk model in patients with non-classical ACM.

Increased 18 F-FAPI-04 Uptake in Vertebral Hemangioma.

ABSTRACT: A 54-year-old man with a history of colectomy for colorectal cancer and subsequent liver metastasectomy underwent 18 F-FDG PET/CT and 18 F-FAPI-04 PET/CT scans to evaluate possible hepatic metastasis revealed by contrast-enhanced MRI. Both studies showed similarly increased uptake in liver metastases, and 18 F-FDG detected a metastatic lung nodule. Furthermore, the images showed an incidental finding of increased uptake of 18 F-FAPI-04 in the L3 vertebral, which was not 18 F-FDG-avid. A review of the patient's previous CT and MRI scans suggests vertebral hemangioma.

Sub-minute acquisition with deep learning-based image filter in the diagnosis of colorectal cancers using total-body 18F-FDG PET/CT.

BACKGROUND: This study aimed to retrospectively evaluate the feasibility of total-body 18F-FDG PET/CT ultrafast acquisition combined with a deep learning (DL) image filter in the diagnosis of colorectal cancers (CRCs). METHODS: The clinical and preoperative imaging data of patients with CRCs were collected. All patients underwent a 300-s list-mode total-body 18F-FDG PET/CT scan. The dataset was divided into groups with acquisition durations of 10, 20, 30, 60, and 120 s. PET images were reconstructed using ordered subset expectation maximisation, and post-processing filters, including a Gaussian smoothing filter with 3 mm full width at half maximum (3 mm FWHM) and a DL image filter. The effects of the Gaussian and DL image filters on image quality, detection rate, and uptake value of primary and liver metastases of CRCs at different acquisition durations were compared using a 5-point Likert scale and semi-quantitative analysis, with the 300-s image with a Gaussian filter as the standard. RESULTS: All 34 recruited patients with CRCs had single colorectal lesions, and the diagnosis was verified pathologically. Of the total patients, 11 had liver metastases, and 113 liver metastases were detected. The 10-s dataset could not be evaluated due to high noise, regardless of whether it was filtered by Gaussian or DL image filters. The signal-to-noise ratio (SNR) of the liver and mediastinal blood pool in the images acquired for 10, 20, 30, and 60 s with a Gaussian filter was lower than that of the 300-s images (P < 0.01). The DL filter significantly improved the SNR and visual image quality score compared to the Gaussian filter (P < 0.01). There was no statistical difference in the SNR of the liver and mediastinal blood pool, SUVmax and TBR of CRCs and liver metastases, and the number of detectable liver metastases between the 20- and 30-s DL image filter and 300-s images with the Gaussian filter (P > 0.05). CONCLUSIONS: The DL filter can significantly improve the image quality of total-body 18F-FDG PET/CT ultrafast acquisition. Deep learning-based image filtering methods can significantly reduce the noise of ultrafast acquisition, making them suitable for clinical diagnosis possible.

Incidental Finding of Intervertebral Disc Herniation With Increased 18F-FAPI-04 Uptake in a Healthy Volunteer.

ABSTRACT: A 44-year-old healthy volunteer received an 18F-FAPI-04 scan for a normal biodistribution and dosimetry study. An incidental finding of an increased uptake of the radiotracer at the L4/5 subarticular disc herniation was noted, and a subsequent MRI scan confirmed the degenerative nature of the lesion.

Artificial intelligence-quantified tumour-lymphocyte spatial interaction predicts disease-free survival in resected lung adenocarcinoma: A graph-based, multicentre study.

BACKGROUND AND OBJECTIVE: A high degree of lymphocyte infiltration is related to superior outcomes amongst patients with lung adenocarcinoma. Recent evidence indicates that the spatial interactions between tumours and lymphocytes also influence the anti-tumour immune responses, but the spatial analysis at the cellular level remains insufficient. METHODS: We proposed an artificial intelligence-quantified Tumour-Lymphocyte Spatial Interaction score (TLSI-score) by calculating the ratio between the number of spatial adjacent tumour-lymphocyte and the number of tumour cells based on topology cell graph constructed using H&E-stained whole-slide images. The association of TLSI-score with disease-free survival (DFS) was explored in 529 patients with lung adenocarcinoma across three independent cohorts (D1, 275; V1, 139; V2, 115). RESULTS: After adjusting for pTNM stage and other clinicopathologic risk factors, a higher TLSI-score was independently associated with longer DFS than a low TLSI-score in the three cohorts [D1, adjusted hazard ratio (HR), 0.674; 95% confidence interval (CI) 0.463-0.983; p = 0.040; V1, adjusted HR, 0.408; 95% CI 0.223-0.746; p = 0.004; V2, adjusted HR, 0.294; 95% CI 0.130-0.666; p = 0.003]. By integrating the TLSI-score with clinicopathologic risk factors, the integrated model (full model) improves the prediction of DFS in three independent cohorts (C-index, D1, 0.716 vs. 0.701; V1, 0.666 vs. 0.645; V2, 0.708 vs. 0.662) CONCLUSIONS: TLSI-score shows the second highest relative contribution to the prognostic prediction model, next to the pTNM stage. TLSI-score can assist in the characterising of tumour microenvironment and is expected to promote individualized treatment and follow-up decision-making in clinical practice.

Multiparametric cardiovascular magnetic resonance characteristics and dynamic changes in asymptomatic heart-transplanted patients.

OBJECTIVES: To describe the dynamic changes in cardiac deformation and tissue characteristics using cardiac magnetic resonance (CMR) in asymptomatic patients during 12 months after heart transplantation (HT). METHODS: From April 2020 to January 2021, 21 consecutive HT patients without clinical symptoms were included in this prospective study. Multiparametric CMR was performed at 3, 6, and 12 months after HT. Twenty-five healthy volunteers served as controls. RESULTS: During follow-up, a decline in left ventricular (LV) global radial strain (GRS) (p = 0.020) and right ventricular (RV) global longitudinal strain (GLS) (p < 0.001) and an increase in post-contrast T1 (p = 0.024) and T2 (p < 0.001) in asymptomatic HT patients occurred at 3 months, which normalized at 6 months postoperatively, compared with those in healthy controls. A decline in LVGLS (p < 0.001) and LV global circumferential strain (GCS) (p < 0.001) and an increase in native T1 (p < 0.001), T2 (p < 0.001), and extracellular volume (ECV) (p < 0.001) occurred at 3 months. Although most parameters improved gradually, LVGLS, native T1, and ECV remained abnormal compared with those in healthy controls at 12 months; only T2 and LVGCS were normalized at 6 months and 12 months, respectively. ECV was significantly correlated with LVGLS, LVGCS, and LVGRS. CONCLUSION: Cardiac deformation and tissue characteristics were abnormal early after HT, although the patients were clinically asymptomatic. The dynamic changes in CMR characteristics demonstrate a gradual recovery of myocardial injury associated with transplantation during the first 12 months after HT. KEY POINTS: • Multiparametric CMR can detect the dynamic changes of transplantation-associated myocardial injury. • Post-contrast T1, T2, LVGRS, and RVGLS values are normalized at 6 months after HT. • Native T1, ECV, and LVGLS values remain abnormal compared with those in healthy controls at 12 months after HT.

Development and evaluation of a radiomics model of resting 13N-ammonia positron emission tomography myocardial perfusion imaging to predict coronary artery stenosis in patients with suspected coronary heart disease.

Background: Coronary angiography (CAG) is usually performed in patients with coronary heart disease (CHD) to evaluate the coronary artery stenosis. However, patients with iodine allergy and renal dysfunction are not suitable for CAG. We try to develop a radiomics machine learning model based on rest 13N-ammonia (13N-NH3) positron emission tomography (PET) myocardial perfusion imaging (MPI) to predict coronary stenosis. Methods: Eighty-four patients were included with the inclusion criteria: adult patients; suspected CHD; resting MPI and CAG were performed; and complete data. Coronary artery stenosis >75% were considered to be significant stenosis. Patients were randomly divided into a training group and a testing group with a ratio of 1:1. Myocardial blood flow (MBF), perfusion defect extent (EXT), total perfusion deficit (TPD), and summed rest score (SRS) were obtained. Myocardial static images of the left ventricular (LV) coronary segments were segmented, and radiomics features were extracted. In the training set, the conventional parameter (MPI model) and radiomics (Rad model) models were constructed using the machine learning method and were combined to construct a nomogram. The models' performance was evaluated by area under the curve (AUC), accuracy, sensitivity, specificity, decision analysis curve (DCA), and calibration curves. Testing and subgroup analysis were performed. Results: MPI model was composed of MBF and EXT, and Rad model was composed of 12 radiomics features. In the training set, the AUC/accuracy/sensitivity/specificity of the MPI model, Rad model, and the nomogram were 0.795/0.778/0.937/0.511, 0.912/0.825/0.760/0.936 and 0.911/0.865/0.924/0.766 respectively. In the testing set, the AUC/accuracy/sensitivity/specificity of the MPI model, Rad model, and the nomogram were 0.798/0.722/0.659/0.841, 0.887/0.810/0.744/0.932 and 0.900/0.849/0.854/0.841 respectively. The AUC of Rad model and nomogram were significantly higher than that of MPI model. The DCA curve also showed that the clinical net benefit of the Rad model and nomogram was similar but greater than that of MPI model. The calibration curve showed good agreement between the observed and predicted values of the Rad model. In the subgroup analysis of Rad model, there was no significant difference in AUC between subgroups. Conclusions: The Rad model is more accurate than the MPI model in predicting coronary stenosis. This noninvasive technique could help improve risk stratification and had good generalization ability.

Clinical utility of 18F-FDG PET/CT imaging in patients with pulmonary artery sarcoma.

BACKGROUND: Pulmonary artery sarcoma (PAS) is a rare and fatal malignancy. Due to the lack of specific clinical and radiological features, PAS is always misdiagnosed as pulmonary thromboembolism (PTE). This study aimed to investigate 18F-FDG PET/CT in distinguishing PAS from PTE, and analyze its correlation with clinical and radiological findings and outcome of PAS. METHODS: Clinical, contrast-enhanced CT, and 18F-FDG PET/CT characteristics of 14 patients with PAS and 33 patients with PTE were retrospectively reviewed. The correlation between PET/CT metabolic parameters vs. clinical and CT findings was investigated in patients with PAS. The overall survival (OS) was analyzed in PAS patients. RESULTS: The SUVmax of PAS (median: 8.0, range 3.0-17.2) was significantly higher than PTE (1.8[0.8-3.7]) (P < 0.001), and at a cutoff value of 2.9, the sensitivity and specificity were 100.0% and 93.9%, respectively. Compared with PTE, PAS more frequently occurred in younger population (P = 0.011), involved pulmonary trunk (P < 0.001), and displayed higher enhanced CT (P < 0.001) and ΔCT (enhanced CT compared to non-enhanced CT) (P < 0.001) values. SUVmax of PAS was associated with tumor staging (P = 0.022) and enhanced CT (P = 0.013) and ΔCT (P = 0.005) values. The median OS of PAS patients was 10.5 months, and 12-month and 24-month OS rates were 58.0% and 12.0%, respectively. Only D-dimer level (P = 0.038) and tumor staging (P = 0.019) were associated with OS. CONCLUSIONS: Most PAS displayed high glucometabolism, and SUVmax of 18F-FDG PET/CT was useful in distinguishing PAS from PTE.

Development and validation of an MRI-based nomogram for the preoperative prediction of tumor mutational burden in lower-grade gliomas.

Background: High tumor mutational burden (TMB) is an emerging biomarker of sensitivity to immune checkpoint inhibitors. In this study, we aimed to determine the value of magnetic resonance (MR)-based preoperative nomogram in predicting TMB status in lower-grade glioma (LGG) patients. Methods: Overall survival (OS) data were derived from The Cancer Genome Atlas (TCGA) and then analyzed by using the Kaplan-Meier method and time-dependent receiver operating characteristic (tdROC) analysis. The magnetic resonance imaging (MRI) data of 168 subjects obtained from The Cancer Imaging Archive (TCIA) were retrospectively analyzed. The correlation was explored by univariate and multivariate regression analyses. Finally, we performed tenfold cross validation. TMB values were retrieved from the supplementary information of a previously published article. Results: The high TMB subtype was associated with the shortest median OS (high vs. low: 50.9 vs. 95.6 months, P<0.05). The tdROC for the high-TMB tumors was 74% (95% CI: 61-86%) for survival at 12 months, and 71% (95% CI: 60-82%) for survival at 24 months. Multivariate logistic regression analysis confirmed that three risk factors [extranodular growth: odds ratio (OR): 8.367, 95% CI: 3.153-22.199, P<0.01; length-width ratio ≥ median: OR: 1.947, 95% CI: 1.025-3.697, P<0.05; frontal lobe: OR: 0.455, 95% CI: 0.229-0.903, P<0.05] were significant independent predictors of high-TMB tumors. The nomogram showed good calibration and discrimination. This model had an area under the curve (AUC) of 0.736 (95% CI: 0.655-0.817). Decision curve analysis (DCA) demonstrated that the nomogram was clinically useful. The average accuracy of the tenfold cross validation was 71.6% for high-TMB tumors. Conclusions: Our results indicated that a distinct OS disadvantage was associated with the high TMB group. In addition, extranodular growth, nonfrontal lobe tumors and length-width ratio ≥ median can be conveniently used to facilitate the prediction of high-TMB tumors.

Langerhans cell histiocytosis presenting as an isolated brain tumour: A case report.

BACKGROUND: Langerhans cell histiocytosis (LCH) is a rare proliferative histiocyte disorder. It can affect any organ or system, especially the bone, skin, lung, and central nervous system (CNS). In the CNS, the hypothalamic-pituitary is predominantly affected, whereas the brain parenchyma is rarely affected. LCH occurring in the brain parenchyma can be easily confused with glioblastoma or brain metastases. Thus, multimodal imaging is useful for the differential diagnosis of these intracerebral lesions and detection of lesions in the other organs. CASE SUMMARY: A 47-year-old man presented with a headache for one week and sudden syncope. Brain computed tomography (CT) and magnetic resonance imaging showed an irregularly shaped nodule with heterogeneous enhancement. On 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/CT, a nodule with 18F-FDG uptake and multiple cysts in the upper lobes of both lungs were noted, which was also confirmed by high-resolution CT. Thus, the patient underwent surgical resection of the brain lesion for further examination. Postoperative pathology confirmed LCH. The patient received chemotherapy after surgery. No recurrence was observed in the brain at the 12-mo follow-up. CONCLUSION: Multimodal imaging is useful for evaluating the systemic condition of LCH, developing treatment plans, and designing post-treatment strategies.

Diagnostic challenges in primary cardiac lymphoma, the opportunity of 18F-FDG PET/CT integrated with contrast-enhanced CT.

BACKGROUND: The purpose of this study was to retrospectively evaluate the value of 18F-FDG PET/CT integrated with contrast-enhanced CT (CECT) in the differential diagnosis of primary cardiac lymphomas (PCLs) and primary cardiac angiosarcomas (PCAs). METHODS: Clinical and imaging data of patients with PCLs and PCAs were collected. All patients underwent preoperative 18F-FDG PET/CT and thoracic CECT. The enhancement pattern and tumor morphology were analyzed using CECT images. The intensity- and volume-based PET parameters of cardiac lesions were analyzed. The performance characteristics of all parameters were assessed. RESULTS: Nine patients with PCL and eight patients with PCA were analyzed. There were significant differences in SUVmax (t = 3.790, P = .002), SUVmean (t = 4.273, P = .001), metabolic tumor volume (U = 13.00, P = .027), tumor-to-liver ratio (U = 10.00, P = .011), and total lesion glycolysis (U = 4.0, P = .001) between PCLs and PC18As. There were significant differences in the enhancement pattern of tumors (P = .002) and tumor morphology (P = .015). The combination of F-FDG PET/CT and CECT improved the diagnostic accuracy, and the combination cutoff (SUVmean > 5.17) could reach 100%, but the difference was not statistically significant (P > .05). CONCLUSION: The intensity- and volume-based PET parameters of PCL were significantly higher than those of PCA. The enhancement pattern and tumor morphology were also different. According to these characteristics, the two most common types of primary cardiac malignancies can be differentiated.

Combined PET/CT with thoracic contrast-enhanced CT in assessment of primary cardiac tumors in adult patients.

BACKGROUND: 18F-FDG PET/CT is a key molecular imaging modality to noninvasively assess and differentiate benign and malignant cardiac tumors. However, few benign cardiac tumors can be characterized by increased 18F-FDG uptake, which makes differential diagnosis difficult. This study sought to retrospectively evaluate whether combined 18F-FDG PET/CT with thoracic contrast-enhanced CT (CECT) helps in assessing primary cardiac tumors in adult patients, compared with CECT or PET/CT alone. METHODS: Forty-six consecutive patients who were diagnosed as primary cardiac tumors were enrolled. All patients underwent 18F-FDG PET/CT followed by thoracic CECT before biopsy or surgery. Visual qualitative interpretation and quantitative analysis were performed, and diagnostic performance was evaluated. RESULTS: More than half (16/29) of benign tumors exhibited with mild 18F-FDG uptake. There were significant differences in 18F-FDG uptake and the degree of absolute enhancement between benign and malignant tumors (P < 0.001). The combination of two modalities improved the specificity from 79 to 93%, the positive predictive value from 73 to 89%, and the accuracy of diagnosis from 85 to 93%. There were significant differences between PET/CT alone or thoracic CECT alone and combined modalities (P = 0.034 and P = 0.026, respectively). The combination with the optimal SUVmax cutoff value generated 94% sensitivity, 100% specificity, 97% negative predictive values, 100% positive predictive values, and 98% accuracy rates. CONCLUSIONS: Combining 18F-FDG PET/C with thoracic CECT significantly improved specificity and accuracy compared to CECT or PET/CT alone in detecting tumors. This combination of diagnostic imaging is effective in differentiating malignant from benign masses.