Incorporating a sulfur (VI)-fluoride exchange (SuFEx) chemistry-based linker, FAPI-based covalent targeted radioligand (CTR) showed better tumor binding affinity and longer retention time than FAPI-04 in animal studies. This study for the first time compared the lesion detection efficacy of [⁶⁸Ga]Ga-CTR-FAPI PET/CT and [⁶⁸Ga]Ga-FAPI-04 PET/CT in a radioiodine-refractory differentiated thyroid cancer clinical cohort. A single-center prospective comparative study was conducted, enrolling 40 RAIR-DTC patients with distant metastases. All patients underwent sequential [⁶⁸Ga]Ga-FAPI-04 PET/CT and [⁶⁸Ga]Ga-CTR-FAPI PET/CT examinations at a 24–48 h interval. Two experienced nuclear medicine physicians performed blinded visual analysis of the images to assess lesion detection status. Semi-quantitative analysis included the measurement of maximum standardized uptake value (SUVmax) and tumor-to-background ratio (TBR) of lesions in different anatomical regions. The reference standard for lesion confirmation was a combination of conventional imaging, histopathological results (when feasible), and long-term clinico-radiological follow-up. The detection performances of the two imaging modalities were compared at the patient and lesion levels. Of the 40 enrolled patients, 37 had detectable metastatic lesions on both imaging modalities. Two patients had lesions exclusively detected by [⁶⁸Ga]Ga-CTR-FAPI PET/CT. [⁶⁸Ga]Ga-CTR-FAPI PET/CT achieved superior visual detection performance in 17.5
To investigate the feasibility of 2-h-delayed total-body [18F]FDG PET/CT for detecting vascular inflammation after concurrent chemoradiotherapy (CCRT) in head-and-neck-cancer (HNC) patients and to exploratorily assess its association with cardiovascular-related events (CVRE). Twenty-four HNC patients underwent 2-h total-body [18F]FDG PET/CT before and 3 months after CCRT and were followed for CVRE. Vascular inflammation was evaluated across eleven arterial segments. Slice-based mean standardized uptake values (SUVmean) were normalized to the superior vena cava (SVC) to derive the target-to-background ratio (TBRmean), and segmental averages (avgTBRmean) were calculated. Pre- and post-CCRT avgTBRmean were compared, and the relative difference (RD-avgTBRmean) was analyzed for association with radiation dose and CVRE. Post-CCRT PET demonstrated increased avgTBRmean in all arterial segments, with significant increases in the carotid arteries (left: 1.32 vs 1.20, P < 0.001; right: 1.34 vs 1.24, P = 0.018), subclavian arteries (left: 1.20 vs 1.14, P = 0.022; right: 1.18 vs 1.10, P = 0.019), and infrarenal abdominal aorta (1.08 vs 0.96, P < 0.001). Mean radiotherapy dose correlated with both post-CCRT avgTBRmean (r = 0.289, P = 0.002) and RD-avgTBRmean (r = 0.251, P = 0.008). Patient-based average RD-avgTBRmean was higher in patients with CVRE (12.1
International guidelines recommend assessment for bone metastases in patients with high-risk prostate cancer (PC) and those with unfavourable intermediate-risk disease. These recommendations are largely based on studies using planar bone scintigraphy. We aimed to assess the diagnostic accuracy of [18F]sodium fluoride ([18F]NaF) PET/CT in newly diagnosed PC. We also evaluated the clinical utility of routine bone imaging in patients with unfavourable intermediate-risk disease and International Society of Urological Pathology grade group (ISUP GG) 3. This retrospective single-center study included 734 consecutive patients with newly diagnosed PC who underwent [18F]NaF PET/CT for primary staging. Patients were classified according to the current European Association of Urology risk classification, with the intermediate-risk subgroup restricted to patients with ISUP GG 3. All scan reports were retrospectively reviewed, and patient-level findings regarding bone metastases were validated against a reference standard based on follow-up imaging and clinical data. Sensitivity, specificity, and predictive values were calculated. Of the 734 patients, 607 (83
Accurate recognition of high-grade dysplasia (HGD) and early invasive carcinoma (IC) within colorectal polyps is essential for selecting the preferred local resection technique. However, optical endoscopic diagnosis can be challenging, particularly in large and advanced polyps. This study investigates whether carcinoembryonic antigen (CEA)-targeted near-infrared fluorescence (NIRF) imaging can distinguish polyps containing HGD/IC from polyps solely containing low-grade dysplasia (LGD), given prior evidence of CEA overexpression in HGD/IC relative to LGD. Patients scheduled for local en-bloc endoscopic resection of advanced rectal polyps were included in the study and received 5 mg or 10 mg intravenous SGM-101, a CEA-targeted fluorescent agent. In vivo imaging was performed using a rigid Quest-Olympus NIRF-endoscope, followed by ex vivo whole-specimen and bread-loaf imaging using the PEARL imaging system. The primary endpoint was the NIRF tumour-to-low-grade-dysplasia ratio (TDR; HGD/IC divided by LGD) performed on bread loafs, as this method enabled direct pathological correlation. Secondary endpoints included dose-finding as well as sensitivity and specificity for detecting HGD/IC. A total of 22 patients were included, with 9/22 containing LGD only and 13/22 containing HGD/IC. Eleven patients received 10 mg and 11 received 5 mg SGM-101. Ex vivo bread-loaf imaging showed a median (IQR) TDR of 1.7 (1.3–2.9), with higher values in the 10 mg group of 2.5 (2.0-3.5) compared to the 1.3 (1.2–1.6) in the 5 mg group (p = 0.023). The sensitivity for detecting HGD/IC was 86
PSMA PET/CT has transformed the detection of nodal recurrence after radical prostatectomy, yet real-world evidence on long-term outcomes of PSMA PET/CT-guided salvage elective nodal radiotherapy (ENRT) remains limited. This study evaluated oncological outcomes of PSMA PET/CT-guided salvage ENRT in a bi-institutional cohort with extended follow-up. We retrospectively analysed 179 patients who received PSMA PET/CT-based ENRT for nodal recurrence after radical prostatectomy at two tertiary centres between 2014 and 2024. Patients with pelvic and/or paraaortic lymph node metastases were included. The primary endpoint was metastasis-free survival (MFS); secondary endpoints included biochemical progression-free survival (BPFS) and overall survival (OS). Survival outcomes were estimated using the Kaplan–Meier method, and prognostic factors were assessed using Cox regression analysis. Of the 179 patients, 104 (58.1
This two-center prospective study sought to evaluate whether D-SPECT-derived myocardial flow reserve (MFR) can identify coronary microvascular disease (CMD) and predict major adverse cardiac events (MACE) in patients who had undergone complete revascularization by percutaneous coronary intervention (PCI). We enrolled 174 patients with angiographically confirmed complete revascularization post-PCI. Global and regional MFR were quantified using dynamic D-SPECT at rest and during pharmacological stress. CMD was defined as global or territorial MFR < 2.0 in the absence of > 50
Prostate-specific membrane antigen (PSMA) PET/CT is widely used in prostate cancer management, but unspecific bone uptake (UBU) remains a diagnostic challenge particularly with [18F]PSMA-1007. Bone uptake metastatic probability (BUMP) score - a composite imaging-clinical model, was compared with PSMA Reporting and Data System (PSMA-RADS, Version 2) for predicting skeletal metastases in UBU. A real-world cohort of [18F]PSMA-1007 PET/CT scans performed at three tertiary cancer centres was retrospectively analysed. Bone lesions with focal PSMA uptake were evaluated. SUVmax, CT-derived mean Hounsfield unit and androgen deprivation therapy status were recorded to calculate BUMP score for each lesion. Lesional PSMA-RADS scores were assigned by experienced radiologists. Ground truth was established using follow-up imaging, prostate-specific antigen (PSA) kinetics and multidisciplinary consensus. Receiver operating characteristic (ROC) analyses assessed diagnostic performance. 130 patients (median age 70 years) with 412 bone lesions were analysed; 60.9
The time-dependent contributions of coronary atherosclerotic plaque burden and myocardial ischemia to clinical outcomes in suspected coronary artery disease (CAD) remain uncertain. This study aimed to evaluate the temporal associations of quantitatively assessed plaque burden and ischemia with cardiovascular events. We studied 1,385 patients with suspected CAD who underwent coronary computed tomography angiography (CCTA) and [15O]H₂O positron emission tomography (PET) perfusion imaging. Plaque burden was measured as percent atheroma volume (PAV) using AI-based CCTA analysis. Myocardial perfusion was evaluated by regional hyperemic myocardial blood flow (hMBF) using PET. Adjusted Cox regression models, including both PAV and hMBF, were used to assess associations with a composite outcome (death, non-fatal myocardial infarction, unstable angina) at 3, 6, and 9 years. The median follow-up time was 7.1 years, during which 185 patients (13.4
Variational autoencoders (VAEs) can detect unsupervised anomalies in medical images. We aimed to determine whether a VAE could automatically detect anomalies in myocardial perfusion SPECT (MPS) images. We then interpreted the training and generative processes of the VAE. We trained a VAE on polar maps to learn the variability of normal myocardial perfusion profiles in latent space. The training dataset comprised 3,432 polar map images (49
To compare the diagnostic performance of [18F]FAPI-04 PET/CT with that of [18F]FDG PET/CT in patients with suspected recurrence of breast cancer following surgical treatment. This is a post‑hoc analysis of data from a prospective single-center clinical trial. Patients with clinical suspicion of recurrence of breast cancer after surgery were consecutively enrolled and underwent both [18F]FDG and [18F]FAPI-04 PET/CT. Paired comparisons of sensitivity and accuracy were performed using McNemar’s test. Differences in semi-quantitative parameters, including maximum standardized uptake value (SUVmax) and tumor-to-background ratio (TBR), were assessed using the Wilcoxon signed-rank test. A total of 44 patients with 880 lesions were included, of whom 40 patients (782 lesions) were confirmed to have recurrent disease. Compared with [18F]FDG PET/CT, [18F]FAPI-04 PET/CT showed higher sensitivity and accuracy across most metastatic sites. The differences were most pronounced for lymph node, pleural, and bone metastases, with significantly higher sensitivity (98.7
Visceral adipose tissue (VAT) has been identified as a risk factor for Alzheimer’s disease (AD). This study aimed to investigate the associations between glucose metabolism in VAT and subcutaneous adipose tissue (SAT) with abnormalities in large-scale brain metabolic networks and cognitive impairment in patients with AD. Ninety-eight patients with AD and 51 normal controls (NCs) underwent total-body 18F-FDG PET/CT examination. Glucose metabolic activity in VAT and SAT was quantified using lean body mass-corrected standardized uptake values (SULs). Independent component analysis (ICA) was applied to brain PET images to identify large-scale metabolic networks, from which subject-specific metabolic load scores were derived. A default mode network (DMN)-centered metabolic expression concordance (DMN-MEC) index was further derived to characterize individual-level relative metabolic expression patterns between the DMN and other large-scale brain networks. Group differences in adipose tissue metabolism and brain metabolic network metrics were examined. Within the AD group, correlations among abdominal adipose tissue metabolism, DMN-MEC index, and cognitive performance were assessed. Compared with NCs, patients with AD showed significantly increased glucose metabolism in both VAT and SAT, accompanied by reduced metabolic load scores in the DMN, dorsal attention network (DAN), frontoparietal network (FPN), and sensorimotor network (SMN), and lower global DMN-MEC. Correlation analyses within the AD group showed that the DMN metabolic load score was significantly positively correlated with the metabolic load scores of multiple other networks. Furthermore, VAT metabolism was significantly negatively associated with the global DMN-MEC index, whereas SAT metabolism showed no such association. VAT metabolic activity was also negatively correlated with Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores. In contrast, DMN metabolic load and global DMN-MEC index showed positive associations with cognitive performance. These findings revealed concomitant abdominal adipose tissue metabolic dysfunction and disruption of large-scale brain metabolic network expression in AD. Importantly, higher VAT metabolism was associated with lower global DMN-MEC and poorer cognitive performance.
This study aimed to evaluate the value of integrated 18F-NOTA-FAPI-04 PET/MRI for CAS-defined clinical activity assessment in thyroid-associated ophthalmopathy (TAO) by investigating the correlation between PET- and multi-parametric MRI-derived features and their predictive performance. A total of 33 TAO participants were prospectively enrolled and underwent intergrated 18F-NOTA-FAPI-04 PET/MRI. According to the Clinical Activity Score (CAS), Eyes were classified as active (CAS ≥ 3) or inactive (CAS<3). For patient-level analysis, participants were classified as inactive only when both eyes were inactive; otherwise, they were classified as active. PET-derived parameters (maximum standardized uptake value [SUVmax], mean standardized uptake value [SUVmean], metabolic tumor volume [MTV], and total lesion FAPI uptake [TLF]), as well as first-order features (mean, minimum, maximum, median, skewness, and kurtosis) from MRI-derived parametric maps (normalized T2-weighted imaging-derived parameter [T2WI], heterogeneity index [α], distributed diffusion coefficient [DDC], diffusion coefficient [D], true relative blood flow [rBF], mean diffusivity [MD], and mean kurtosis [MK]) were extracted. Repeatability was assessed using the Dice similarity coefficient (DSC) of VOIs delineation and the intraclass correlation coefficient (ICC) for quantitative parameters. Correlation analyses between PET and MRI features, comparisons between active and inactive group, and discriminative performance evaluations of PET, MRI, and combined PET/MRI models were performed at both patient and eye levels. Support vector machine (SVM) and receiver operating characteristic (ROC) analysis were performed to compare discriminative performance. VOIs delineation demonstrated good interobserver and intraobserver agreement, with DSC of 0.850 (95
This study assessed the prognostic value and inter-/intra-observer reliability of three amyloid PET interpretation methods—conventional visual reading, assisted visual interpretation and standardized uptake value ratio (SUVR)-based quantification—for predicting conversion to Alzheimer’s disease (AD). This retrospective longitudinal study included 145 patients with amnestic mild cognitive impairment who underwent amyloid PET and were followed for up to 8 years at a single memory clinic. Two certified nuclear medicine physicians performed structured visual reads and assisted visual interpretations. Semiquantitative SUVR thresholds validated in prior studies were applied as a third method. Inter- and intra-observer agreement was assessed using Cohen’s kappa (κ). Cox regression models estimated the association of conversion to AD in PET-positive versus PET-negative patients for each method, adjusting for age, sex and education. Inter-observer agreement was excellent for structured visual reading (κ = 0.877) and assisted visual interpretation (κ = 0.904). Intra-observer reliability was also high (κ = 0.891 for Reader 1; κ = 0.859 for Reader 2). Consensus agreement for the assisted method reached κ = 0.936. Amyloid PET positivity was strongly associated with progression to AD across all methods. Hazard ratios were highest for assisted visual interpretation (HR = 3.23, 95
Manual quantification of joint metabolism and inflammation with PET is time-consuming and difficult to standardize due to ambiguous joint boundaries. We aimed to develop an automatic joint segmentation method that efficiently and reliably quantifies activity in weight-bearing joints using [18F]fluorodeoxyglucose (FDG) and sodium [18F]fluoride (NaF) PET/computed tomography (PET/CT). Segmentations were generated from CT scans using the TotalSegmentator model. From these, 30 weight-bearing joints were segmented by identifying the region between adjacent bones within a set distance threshold. Scans of healthy volunteers were analyzed (75 with FDG, 80 with NaF). Mean standardized uptake value (SUVmean) was calculated for each joint region, and Pearson correlation analysis was used to evaluate relationships with age and body mass index (BMI). Benjamini–Hochberg false discovery rate (FDR) correction was applied within each tracer–covariate family. The automated approach reduced segmentation time from 30 to 1.5 min per scan. Joint ROI volumes generated independently from the two PET/CT sessions of the same participant were highly concordant (median r = 0.98, median intraclass correlation coefficient 0.94). After false discovery rate correction, NaF uptake was positively correlated with BMI in the thoracic (T3-T6, T7-T8, T9-T11) and lumbosacral (L5-S1) intervertebral discs (IVDs) and in the sacroiliac (SI), hip and knee joints, and positively with age in the cervical IVDs (C1-C2, C3-C7), with negative age correlations at T4-T5, T6-T7, L1-L2 and in both SI joints (all q < 0.05). FDG uptake was positively correlated with BMI in the IVDs from C1-T6 (other than T1-T2) and T9-S1, in both SI joints, the left hip and both knees, and with age in both knees, and negatively with age at T2-T3 and in both SI joints (all q < 0.05). Associations meeting p < 0.05 but not q < 0.05 are identified in Tables 2, 3, 4 and 5. The positive cervical NaF-age associations arise in the only joints where SUVmean was appreciably correlated with ROI size and are therefore reported as provisional. Our segmentation approach rapidly quantifies joint metabolism and revealed significant associations between PET tracer uptake, BMI, and age. It offers a standardized framework for future PET/CT joint analysis. Cardiovascular Molecular Calcification Assessed by 18 F-NaF PET/CT (CAMONA), ClinicalTrials.gov NCT01724749. https://clinicaltrials.gov/study/NCT01724749 .
Diagnosis of giant cell arteritis (GCA) is challenging and relies mainly on temporal artery biopsy and/or Doppler ultrasound (DUS). Although [18F]FDG PET/CT is the test of choice suspected large vessel (LV)-GCA, its use in cranial artery GCA (C-GCA) detection was previously limited. Digital PET/CT devices have improved resolution and sensitivity for smaller lesions. This international prospective cross-sectional comparative study investigates the diagnostic accuracy of digital PET/CT and DUS in patients with suspected GCA. Patients aged ≥ 50 years with suspected GCA based on classical symptoms and inflammatory markers were enrolled. Exclusion criteria included corticosteroid therapy for > 3 days prior to PET/CT or prior history of vasculitis. PET/CT scans were interpreted independently by two blinded readers using standardized visual grading scales; in case of disagreement, a third blinded reader adjudicated. DUS of the temporal and axillary arteries was performed as standard of care. Temporal artery biopsy was performed at the treating physician’s discretion. Final clinical diagnosis at 6 months served as reference standard. Of 92 enrolled subjects, 8 were excluded as they did not undergo DUS. Eighty-four subjects (mean age: 72 years; mean CRP: 70.7 mg/L) were included in the analysis with mean follow-up of 27 months (range 6–74). GCA was diagnosed in 44/84 patients. PET/CT sensitivity increased from 50.0
Advanced hepatocellular carcinoma (HCC) with portal vein tumour thrombus (PVTT) carries a dismal prognosis. This study evaluated the efficacy and safety of transarterial radioembolisation (TARE) combined with targeted therapy and immune checkpoint inhibitors (ICIs) in patients with HCC and Vp2–Vp4 PVTT, and explored the tumour absorbed dose (TAD) threshold associated with survival benefit. We retrospectively analysed 31 patients with HCC and Vp2–Vp4 PVTT treated with this triplet regimen. Tumour responses were assessed per mRECIST and RECIST 1.1. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method. The optimal TAD cutoff was identified through dose-threshold exploration and internally validated by bootstrap resampling. The objective response rate was 77.4
Relapsed/refractory classical Hodgkin lymphoma (R/R cHL) remains clinically challenging due to substantial heterogeneity in relapse risk. Reliable, non-invasive tools for improved relapse risk stratification are urgently needed to guide individualized therapeutic strategies. In this multicenter retrospective study, 161 patients with R/R cHL from five institutions were included (training cohort: n = 102; validation cohort: n = 59). Clinical and metabolic covariates were assessed at the time of relapsed/refractory disease and baseline 18F-FDG PET/CT before salvage treatment. We developed a deep learning-based Mixture-of-Experts (MoE) framework that integrates four medical foundation models (PET-Diffusion, SAM-Med2D, MedCLIP, and RadFM) to derive a quantitative imaging biomarker (MoEScore) from baseline 18F-FDG PET/CT. A multiparametric model incorporating MoEScore and independent clinical/metabolic predictors was constructed and evaluated using discrimination, calibration, and clinical utility analyses. Model interpretability was assessed using attention visualization, ablation analysis, and pathological correlation. MoEScore demonstrated predictive performance (AUC: 0.861 in training; 0.783 in validation) and remained independently associated with relapse (HR = 11.18, 95
To investigate the association between baseline NETPET score and prognosis in patients with neuroendocrine tumors (NETs) receiving [225Ac]Ac-DOTATATE therapy. This retrospective study included patients with NETs treated with [225Ac]Ac-DOTATATE between November 2021 and March 2025. All patients underwent [18F]F-FDG and [68Ga]Ga-DOTATATE PET within one week before treatment. Up to 10 representative lesions per patient were selected for NETPET scoring. The primary endpoint was progression-free survival (PFS). The relationship between NETPET score and PFS was evaluated using Kaplan–Meier analysis and univariate/multivariate Cox proportional hazards models. Forty-eight patients were enrolled (P1: n = 14, P2–4: n = 22, P5: n = 12). The P1 group achieved significantly better PFS than the P2-4 and P5 groups (2-year PFS rates: 0.83 vs. 0.32 vs. 0.10; log-rank P < 0.0001). Univariate analysis revealed a significant association of NETPET score with PFS (P2–4 vs. P1: HR = 7.07, P = 0.009; P5 vs. P1: HR = 17.0, P < 0.001). Multivariate analysis demonstrated the NETPET score to be independently associated with PFS (P2–4 vs. P1: P = 0.003; P5 vs. P1: P < 0.001). Its predictive value for overall survival was limited (P > 0.05). The NETPET score was independently associated with progression-free survival and may serve as a potential imaging biomarker for pretreatment risk stratification in NET patients receiving [225Ac]Ac-DOTATATE therapy.
Triple negative breast cancer (TNBC) is an aggressive subtype, still with limited therapeutic options. [18F]FDG PET/CT is widely used in TNBC, but evidence regarding its prognostic value remains limited. The TRINE PET study, promoted by the Italian Association of Nuclear Medicine, aimed to evaluate the prognostic relevance and clinical impact of [18F]FDG PET/CT in a large real world TNBC cohort. This retrospective multicenter study included 389 TNBC patients who underwent 707 [18F]FDG PET/CT scans across 23 Italian Nuclear Medicine Units. Clinical settings were baseline staging (n = 257 patients), post neoadjuvant chemotherapy (n = 111 patients), suspected recurrence (n = 144 patients), and advanced metastatic disease (n = 195 patients). Progression free survival (PFS) and overall survival (OS) were assessed using Kaplan–Meier and Cox regression analyses. The influence of [18F]FDG PET/CT on clinical management was evaluated across all settings. During a median follow up of 34 months (1–124), disease progression and death occurred in 39.3
