Despite decades of technical development, dynamic PET and parametric imaging have not yet achieved widespread clinical implementation in oncology, largely due to technical complexity and the limited number of clinical scenarios in which clear additional value over static imaging has been demonstrated. We hypothesized that liver metastases from uveal melanoma-a tumor entity often characterized by low tumor-to-background contrast on static imaging- may represent a particularly promising application for dynamic PET imaging. Accordingly, we aimed to determine whether dynamic Patlak parametric imaging improves lesion detectability and conspicuity compared with standard (50-60 min) and delayed (70-85 min) static standardized uptake value (SUV) imaging. Twenty-six patients with uveal melanoma and a total of 126 tumor lesions, including 58 liver metastases and 68 other metastases, were prospectively enrolled. All patients underwent a 60 min dynamic data acquisition (skull to upper thigh) followed by whole-body [18F]FDG PET/CT imaging at 70 min post-injection. Three image datasets were generated and compared: (1) Direct Patlak Ki parametric images derived from dynamic acquisition at 30-60 min post-injection, (2) standard static SUV images reconstructed from same dynamic acquisition at 50-60 min post-injection (standardSUV), and (3) delayed static SUV images acquired at 70-85 min post-injection (lateSUV). All three image sets were assessed qualitatively for lesion detectability and quantitative analysis was performed for all 126 lesions using tumor-to-background ratio (TBRmean) measurements. No significant differences were observed among the three imaging approaches with respect to the total number of detected tumor lesions. However, one discordant finding was noted: a true-positive liver metastasis was identified on Patlak Ki imaging and subsequently confirmed by MRI, but was not clearly visualized on static SUV images. Qualitatively, for liver and other metastases, Patlak Ki and lateSUV images showed significantly higher TBRmean values than standardSUV, with mean increases of ~ 2.1-2.3-fold for Ki and ~ 1.3-fold for lateSUV. Furthermore, Patlak Ki yielded significantly higher TBRmean than lateSUV (52/58 and 65/68) and standardSUV (57/58 and 67/68) for liver and other metastases, respectively. Although lesion detection rates were not significantly increased, dynamic acquisition with Patlak parametric imaging provided a robust and less timing-dependent method to enhance tumor-to-background contrast compared with static SUV imaging and may yield discordant findings with additional clinical value in selected cases. Overall, Patlak imaging may therefore represent a complementary contrast-optimization approach for evaluating liver metastases from uveal melanoma.
Interaction of gut microbiota (GM) with dietary sugars (glucose, sorbitol) and choline has been transversely implicated in the pathogenesis of multiple chronic diseases. Our aim was to develop functional PET imaging of GM, using a multi-tracer approach to capture bacteria classes involved in sugar fermentation and choline catabolism at their gastrointestinal (GI) location. Adult and young sex-balanced groups of mice underwent oral administration of [18F]FDG, [18F]FDS or [11C]choline ([11C]cho) and repeated PET imaging over 4-5 h. Antibiotics, probiotic or faecal microbiota transplantation (FMT) served to quantify the specific role and site of bacteria action. GM was sequenced ex-vivo; gut histology and metabolic profiles were assessed in subsets. [18F]FDG and [18F]FDS reflected caecum abundance of Clostridia and Bacteroidia fermenters, with [18F]FDG exhibiting strongest and broadest relations. Clearance of [11C]cho from small gut reflected Bacilli and Lactobacilli abundance. In vitro cultures supported these relationships. Urinary 11C-excretion was nearly abolished by antibiotics. PET imaging was able to differentiate and predict gut bacteria classes in mice receiving FMT from two age-extreme human donors. Urinary [18F]FDS excretion reflected small-gut goblet cell activation; high caecum [18F]FDG retention and small gut [11C]cho clearance predicted body glucose use and low systemic inflammation. Imaging of ingested probes is simple and effective to map GM characteristics in situ and the functional crosstalk with host processes in mice in real-time. Our data confirm that the GI ecosystem is highly diversified, pointing to small intestine and caecum GM as dominant players in gut-body handling of our target nutrients.
This study aimed to evaluate a deep-learning (DL)-based framework to automatically perform breast cancer (BC) metabolic staging on [¹⁸F]FDG PET/CT, and to assess agreement among DL-based, nuclear medicine (NM) physician-based, and clinical staging. A total of 403 histologically confirmed BC patients who underwent whole-body staging [¹⁸F]FDG PET/CT were retrospectively included. All [18F]FDG avid lesions suspected of malignancy were segmented by an NM physician and classified into four key tumor regions: primary tumor (pT), regional axillary lymph nodes (ALN), extra-axillary locoregional nodes (extra-ALN), and distant metastases (dM). Data were split into training (n = 303) and testing (n = 100) sets using a stratified approach. Class-specific DL segmentation networks were developed. A post-processing pipeline was implemented to derive metabolic TNM staging from the DL-based segmentation. Using NM-based and clinical staging segmentation as reference, accuracy, sensitivity, and specificity were computed for T, N, and M. Segmentation performance was evaluated using the Dice coefficient (DC) and lesion detection (LD) metrics. NM-based metabolic staging was also compared with clinical staging. DL-based staging showed concordance with NM-based/clinical staging of 75/62%, 87/74%, and 83/82% for T, N, and M, respectively. For N3 (presence of extra-ALN) and M1 (presence of dM), where [¹⁸F]FDG PET/CT is particularly relevant, sensitivity/specificity of DL-based (NM-based reference) were 0.86/0.96, and 0.97/0.78, respectively. Segmentation performance was good to excellent for pT, ALN, and dM (median DC ≥ 0.83 and LD ≥ 0.78), and moderate for extra-ALN (median DC = 0.63 and LD ≥ 0.71). NM-based metabolic staging agreed with clinical staging in 63%, 80%, and 99% of cases for T, N, and M, respectively. Although expert supervision remains essential, the developed DL-based framework demonstrates potential as a supportive tool for metabolic staging in BC patients, facilitating a workflow-efficient [¹⁸F]FDG PET/CT-based staging assessment.
Amyloid-β and tau deposition follow distinct spatial and temporal trajectories across the Alzheimer's disease (AD) continuum. Amyloid accumulation occurs early in the disease course, whereas tau pathology is more closely associated with neurodegeneration and clinical progression. Characterizing stage-specific regional divergence between amyloid and tau deposition may refine biomarker-based disease staging and improve prognostic assessment. We analyzed participants from the BATON study who underwent amyloid PET with 18F-flutemetamol, tau PET with 18F-MK-6240, and 3D MRI within a three-month interval. Participants were classified into cognitively normal amyloid-negative controls (CNA, n = 101) and the AD continuum (n = 102), comprising preclinical AD (PCA, n = 47), mild cognitive impairment due to AD (MCA, n = 24), and AD dementia (ADD, n = 31). Standardized uptake value ratios (SUVRs) were calculated using the Centiloid and CenTauR frameworks, and voxel-wise tau-to-amyloid ratio (TAR) images were generated. Voxel-wise and region-of-interest analyses were performed to compare regional patterns of amyloid deposition, tau accumulation, and TAR across disease stages. Amyloid deposition was already widespread at the PCA stage, involving the frontal, posterior cingulate/precuneus, and temporal cortices. In contrast, tau deposition in PCA was largely confined to the medial temporal lobe. With progression to MCA and ADD, tau burden increased substantially and extended to the lateral temporal, parietal, and frontal cortices. TAR analysis demonstrated high values in the medial temporal cortex at the PCA stage, followed by decreasing TAR in frontal regions during MCA and a tau-dominant neocortical pattern in ADD. Amyloid and tau exhibit distinct and stage-dependent regional dissociation across the AD continuum. TAR imaging effectively captures this divergence, reflecting early medial temporal tau predominance and subsequent neocortical tau expansion. These findings support the utility of integrated amyloid-tau PET metrics for refined disease staging and longitudinal therapeutic monitoring.
Clinical prognostication and decision-making in IDH-mutant glioma is increasingly complex, especially with new targeted treatment options like IDH-inhibitors. Individual patient risk stratification for better treatment planning is needed; however, standard prognostic models rely on clinical and histologic parameters as well as MRI, which may not fully reflect the tumor's biological behavior. Positron emission tomography (PET) imaging of the 18 kDa translocator protein (TSPO) is known as surrogate marker of activated microglia and macrophages and enables non-invasive assessment of the tumor microenvironment and peri-/intratumoral inflammation as well as TSPO-positive tumor cells. The aim of this study was to investigate TSPO-PET imaging in IDH-mutant glioma and its association with outcome. In this monocentric, retrospective study, 46 patients with newly diagnosed IDH-mutant glioma who had undergone TSPO-PET imaging with [¹⁸F]GE180 prior to any therapeutic intervention were included. Quantitative PET parameters including mean and maximum standardized uptake values (SUVmax, SUVmean) and the respective PET-positive tumor volumes were evaluated for their association with clinical data and time to next intervention (TTNI), and overall survival (OS). The cohort consisted of 27 patients (58.7%) with astrocytoma, IDH-mutant (median age 36 years (30-51)) and 19 patients (41.3%) with oligodendroglioma, IDH-mutant and 1p/19q-codeleted (median age 41 years (36-48)). High SUVmax on TSPO-PET imaging was associated with shorter TTNI, and OS (p = 0.0118 and p = 0.0459, respectively). In multivariate analyses adjusting for age, KPS, WHO grade, FET-PET-positive volume, and tumor volume on contrast-enhanced MRI, the TSPO-PET-positive volume was associated with TTNI (hazard ratio (HR) = 1.037, 95% CI: 1.009-1.064, p = 0.0106). This study highlights the potential prognostic utility of TSPO-PET imaging in newly diagnosed IDH-mutant glioma. Our findings support the inclusion of PET imaging in future clinical trials to develop imaging-based risk models for better prognostication and individualized treatment guidance.
Little is known about predictors of response to radionuclide therapy with PSMA-ligands in patients with [18F]FDG-positive metastatic castration-resistant prostate cancer (mCRPC). We assessed the correlation between baseline characteristics, including dual tracer PET parameters, and response to [177Lu]Lu-PSMA-I&T in a cohort of patients with [18F]FDG-positive mCRPC. Prognostic factors related to progression-free survival (PFS) and overall survival (OS) were also investigated. mCRPC patients who underwent [68Ga]Ga-PSMA-11 and [18F]FDG PET/CT prior to [177Lu]Lu-PSMA-I&T were retrospectively evaluated. Only [18F]FDG-positive patients were included in the analysis. A semi-automatic segmentation tool was applied to measure the whole-body maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), metabolic tumor volume (MTV), and total lesion uptake (TLU) on both PET/CTs. PSA response was defined as ≥ 30% and ≥ 50% decline. Imaging response, assessed two months after the last cycle, was defined according to RECIST 1.1 and/or PSMA PET progression (PPP) criteria. Clinical, biochemical, and imaging-based factors were correlated to response to treatment, PFS, and OS. Twenty-five [18F]FDG-positive patients who received [177Lu]Lu-PSMA-I&T were included. PSA30 and PSA50 responses were achieved in 11/25 (44%) and in 9/25 (36%) patients, respectively. In the univariate analysis [68Ga]Ga-PSMA-11 SUVmean (p = 0.022) and [68Ga]Ga-PSMA/[18F]FDG SUVmean ratio (p = 0.021) were significantly associated with PSA30 response. [68Ga]Ga-PSMA-11 SUVmean was also significant in the multivariate model. ROC analysis indicated an optimal [68Ga]Ga-PSMA-11 SUVmean cutoff value of 10.23 (AUC = 0.741), and a best discriminating [68Ga]Ga-PSMA/[18F]FDG SUVmean cutoff ratio of 2.08 (AUC = 0.727). In the univariate analysis for radiological PFS (rPFS), high ALP (p = 0.023), [68Ga]Ga-PSMA-11 MTV (p = 0.011), [68Ga]Ga-PSMA-11 TLU (p = 0.015), and [18F]FDG MTV (p = 0.013) were significantly associated with shorter rPFS. [68Ga]Ga-PSMA-11 MTV showed a borderline association with rPFS in the multivariate model (p = 0.061). Hemoglobin levels (p = 0.008), ALP (p = 0.018) and PSA (p = 0.023) values before treatment were associated with OS, as well as [68Ga]Ga-PSMA-11 MTV (p = 0.003), [68Ga]Ga-PSMA-11 TLU (p = 0.025), and [18F]FDG MTV (p = 0.024). However, no independent predictors of OS were identified in the multivariate analysis. Our preliminary results suggest that a whole-body [68Ga]Ga-PSMA-11 SUVmean higher than 10 and a [68Ga]Ga-PSMA-11/[18F]FDG SUVmean ratio > 2 may serve as useful predictors for identifying patients likely to achieve at least a 30% reduction in PSA levels, even among [18F]FDG-positive mCRPC patients. Furthermore, our findings support the prognostic significance of tumor burden either calculated by imaging-based volumetric parameters or by known biochemical markers of disease.
To enhance patient safety in nuclear medicine (NM) across Europe by operationalising MARLIN recommendations for implementing incident learning systems (ILSs), including barriers/enablers and practical implementation guidance. A mixed‑methods study (combining a survey, semi‑structured interviews, and a targeted literature review) was performed within the MARLIN project. This was a 24‑month initiative conducted under the European Commission's Strategic Agenda for Medical Ionising Radiation Applications (SAMIRA) Action Plan, involving European organisations such as EANM, EIBIR, ESTRO, and EFOMP. Surveys were distributed to Clinical Facilities (CFs), Competent Authorities (CAs), and professional societies (PSs). Interviews were used to explore implementation barriers and examples of good practice. Data were analysed using descriptive statistics and thematic analysis. The study revealed significant variability in the criteria for defining and reporting significant radiation events in NM across Europe. While all surveyed countries had designated authorities for managing reported events, only 11/23 had specific criteria for NM. The study identified key enablers and barriers to ILS implementation, including the need for a just culture to encourage reporting without fear of punitive measures. The guidelines recommended criteria for significant radiation events in NM and the organisation of ILSs. The MARLIN study provides a comprehensive framework for the systematic implementation of ILSs in NM, highlighting the importance of standardised reporting criteria in several categories, multidisciplinary involvement, and a culture of safety. Addressing the identified barriers and promoting a coordinated effort among stakeholders are crucial for enhancing patient safety in NM across Europe.
Non-human imaging using either inanimate phantoms or live animal models is sometimes performed as an alternative to human subjects but involve limitations either in fidelity for the former and ethical considerations for the latter. Plant biology has previously been probed using positron emitting tracers, but the potential for long-axial field-of-view (LAFOV) PET/CT systems with higher sensitivities and longer axial coverage in the imaging of plant biology has not yet been explored. A selection of both ornamental plants and those of agricultural interest were obtained. A method was developed for the safe instillation of radiopharmaceuticals leading to rapid transport kinetics throughout the plant. [18F]FDG was obtained from an in-house cyclotron and [68Ga]Cl3 from an onsite 68Ge/68 Ga generator. The potential for LAFOV PET to probe transport kinetics throughout different vascular compartments was assessed, including for plant models which would not fit within the aFOV of a standard short-axial camera. Several plant models were successfully imaged using both radiopharmaceuticals. Owing to differences in dispersion between [18F]FDG and [68Ga]Cl3 within the phloem and xylem vascular systems, variation for the in vivo biodistribution was observed between the two radiopharmaceuticals. The transport kinetics were successfully imaged and quantified by means of dynamic imaging and the longer axial coverage lent itself to the imaging of larger plant models, such as Helianthus annuus (Sunflower). LAFOV PET/CT systems are feasible for both static and dynamic imaging of different plant models. In vivo biodistribution and kinetics were successfully demonstrated. The longer axial coverage enabled efficient imaging of multiple plants or plants which would not have fitted within the axial FOV of a short-axial PET/CT system.
To characterize the systemic and organ-specific pharmacokinetics (PK) of a novel bis-boron tracer, [18F]BBPA, using total-body PET imaging in comparison with conventional blood sampling. Ten healthy volunteers underwent 60-minute dynamic total-body [18F]BBPA PET, followed by three static scans (up to 240 min p.i.), alongside 11 venous blood sampling. Regions of interest were drawn on PET in their right atrium, superior vena cava (SVC), and inferior vena cava (IVC) to obtain image-derived blood time-activity curves (TACs), as well as in major organs to obtain tissue TACs. PK parameters of [18F]BBPA were assessed using both blood samples and image-derived blood TACs. Additionally, tissue TACs were analyzed for organ-specific PK and fitted with an tissue-compartment models for kinetic rates of [18F]BBPA. [18F]BBPA exhibited rapid clearance (6.58 ± 0.57 L/h, a short elimination half-life (186.48 ± 30.29 min), and a volume of distribution of 29.22 ± 3.52 L. Image-derived PK results were comparable to those obtained from blood sampling, with the relative differences < 13% for SVC and < 15% for IVC. Imaging-derived method captured higher Cmax and shorter Tmax, primarily due to its superior temporal resolution. Organ-specified PK revealed low tissue affinity (partition coefficient < 1.0 in most organs) and minimal metabolic trapping (k3 < 0.06 min- 1 and k2 > K1 in the majority of organs). [18F]BBPA exhibits favorable PK properties, including rapid distribution, low normal-tissue affinity, and quick clearance. Total-body PET-image-derived method provides a reliable, non-invasive alternative to conventional blood sampling while offering additional, detailed organ-level kinetic insights. This is a phase I clinical trial approved by the National Medical Products Administration of China and was registered at www.chinadrugtrials.org.cn (CTR20233997).
This study aims to assess the diagnostic performance of 18F-FDG PET/CT parameters for the preoperative prediction of axillary lymph node (ALN) metastasis in Luminal A-type breast cancer patients, and to investigate the net clinical benefit of combining visual analysis with quantitative metrics. We retrospectively evaluated 279 treatment-naive female patients histopathologically diagnosed with Luminal A type breast cancer who underwent 18F-FDG PET/CT for staging and subsequent ALN sampling between January 2012 and December 2025. Both visual assessment and quantitative parameters-including maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of the primary tumor, as well as axillary SUVmax and the axilla-to-primary SUVmax ratio (SUVr)-were analyzed by two nuclear medicine specialists in consensus. Diagnostic performance was measured using ROC analysis and DeLong's test. The incremental value of the models was evaluated through Net Reclassification Improvement (NRI) and Integrated Discrimination Improvement (IDI), while clinical utility was determined via Decision Curve Analysis (DCA). ALN metastasis was confirmed in 152 (54.5%) patients. All quantitative parameters were significantly higher in the metastatic group (p < 0.001). While expert-based visual analysis showed 84.6% accuracy, axillary SUVmax (AUC: 0.881, 95% CI: 0.841-0.920) significantly outperformed visual assessment (AUC: 0.851, p = 0.031). At a cutoff of 0.93, axillary SUVmax yielded 83.6% sensitivity and 79.5% specificity. The Combined Model, integrating visual and quantitative data, achieved the highest diagnostic power (AUC: 0.889) and was statistically superior to axillary SUVmax alone (p = 0.022). The incorporation of quantitative data correctly reclassified 29% (NRI) of metastatic patients initially reported as false negatives in visual analysis and improved overall discrimination by 41.4% (IDI). DCA revealed that the combined model offered a higher net clinical benefit than standard surgical approaches within a 20-90% risk threshold range. In Luminal A-type breast cancer, objective quantitative 18F-FDG PET/CT parameters and their derived multiparametric models significantly exceed the diagnostic limitations of conventional visual assessment. By providing high net clinical benefit in the surgical decision-making process, the proposed combined model has the potential to serve as a valuable personalized decision support tool for the management of high-risk patients and the de-escalation of invasive surgery in low-risk cohorts.
This study aimed to evaluate the imaging features and prognostic value of metabolic parameters derived from pretreatment 18F-FDG PET in pediatric neuroblastoma (NB) patients, and to establish a prognostic prediction model. This retrospective analysis included pediatric patients with extracranial embryonic solid tumours, notably NB, who underwent pretreatment 18F-FDG PET between Jan 2013 and Sep 2023 (NCT06190574). PET parameters were recorded, including SUVmax, SUVmean and their liver-normalized ratios (SUVmax/liver, SUVmean/liver), TLG, MTV. The diagnostic value of 18F-FDG PET for distinguishing NB were calculated. Correlations between metabolic parameters and clinical variables (age, gender, NSE, LDH, ferritin, INSS, and INRGSS stages) were analyzed. Survival analysis using the Kaplan-Meier method was performed to identify predictors of PFS and OS. A nomogram incorporating variables selected by univariate COX and LASSO regression was created, with its discrimination and calibration assessed. Among 81 patients, 41 were pathologically confirmed as NB, yielding an 18F-FDG PET sensitivity of 92.7% and specificity of 95.0%. Metastasis was associated with all serological markers and PET parameters. TLG and MTV correlated with NSE and LDH. Of the confirmed NB patients, 37 were eligible for inclusion in survival analysis. PFS was associated with age, maximum diameter, SUVmax, TLG, MTV, ferritin, NSE and LDH. OS was significantly influenced by age, maximum diameter, SUVmax, SUVmean SUVmax/liver, SUVmean/liver, TLG, MTV, NSE, LDH. The prognostic model incorporating maximum diameter, MTV and NSE exhibited favorable discrimination and calibration. 18F-FDG PET provides valuable diagnostic and prognostic information for NB. The proposed nomogram integrating maximum diameter, MTV, and NSE serves as a practical tool for assessing patient condition and predicting survival outcomes. NCT06190574.
Radioligand therapy (RLT) targeting somatostatin receptors is an established treatment for advanced neuroendocrine tumors (NETs). While long-term safety data for [¹⁷⁷Lu]Lu-DOTA-TATE monotherapy are increasingly available, evidence regarding late toxicity of tandem RLT combining ⁹⁰Y- and ¹⁷⁷Lu-labeled somatostatin analogues remains limited. We evaluated the long-term safety profile of tandem [⁹⁰Y]Y/[¹⁷⁷Lu]Lu-DOTA-TATE RLT in a large real-world cohort with extended follow-up. This retrospective study included 89 patients with NETs treated between 2002 and 2016 and followed for 9-20 years. Long-term renal, hematological, and hepatic toxicities were assessed. Renal function was analyzed longitudinally using patient-level annual estimated eGFR decline and time-to-event analysis for chronic kidney disease (CKD). Patients undergoing repeated RLT were analyzed separately. Grade ≥ 3 nephrotoxicity was observed in 3.4%. Median annual eGFR decline was - 2.1 mL/min/1.73 m² and was significantly steeper in patients with nephrotoxicity (- 4.2 vs. -1.6 mL/min/1.73 m²/year; p < 0.001). The cumulative incidence of CKD reached 51% at 10 years, while no cases of end-stage renal disease requiring dialysis or transplantation were observed. Grade ≥ 3 thrombocytopenia occurred in 5.6%, and one case of myelodysplastic syndrome was observed after supra-standard cumulative activity. Among patients undergoing repeated tandem RLT (16.9%), no statistically significant excess long-term renal or hematological toxicity was detected. Tandem RLT was associated with low rates of severe late toxicity, even after very prolonged follow-up and repeated treatment courses, although gradual long-term decline in renal function was common. These data provide a rare long-term real-world benchmark for late toxicity of high-energy β-emitter-based RLT and support the long-term feasibility of tandem RLT in selected patients with NETs.
The aim of this study was to investigate the limits of diagnostics and therapy planning for patients with prostate cancer using non-time-of-flight 18F/68Ga-PSMA PET/MRI under clinically challenging imaging conditions with small lesion sizes and low uptake. Lesion detectability and quantification accuracy were evaluated for different acquisition and reconstruction parameters in a systematic phantom study and subsequent on patient data. PET/MRI measurements were performed using a small lesion NEMA phantom. PET data were acquired for nine different activity concentrations (AC). Data of a longer single-bed protocol in the pelvis or a shorter whole-body protocol were reconstructed using relative or absolute scatter correction (SC). PET images were analysed considering a ± 25% deviation range between imaged and true AC as acceptable. Thirteen PSMA-PET/MRI patients with primary lesions or lymph node metastasis < 12 mm in the pelvis were included in this study. The presence of the halo artefact was evaluated in six 18F-PSMA and seven 68Ga-PSMA PET/MRI patients. For 21 lesions (diameter 6.4-12.3 mm) in total, the AC was quantified. For both radiotracers, the 9.7 mm sphere was still visible at 0.16 kBq/mL with emission times > 40 min. The 3.7 mm sphere was only detectable at 22 kBq/mL with emission times > 4 min. All spheres ≥ 6.5 mm provide acceptable quantification at an AC of 1.32 kBq/mL for 18F PET/MRI protocols of ≥ 12 min and 2.75 kBq/mL for 68Ga PET/MRI protocols. In phantom data, no halo artefact was observable and different SC methods had no impact on quantification. 4/6 18F-PSMA patients and 7/7 68Ga-PSMA patients showed a halo around the bladder using relative SC, which could be reduced in all patients using absolute SC. Comparing the minimum quantifiable AC (MQAC) from in the phantom study as a threshold to the patient data, all lesions provided acceptable quantification with values > MQAC (AC 3.3-108.5 kBq/mL) for equal reconstruction and acquisition parameters. The results demonstrated that the detection of lesions in the sub-centimetre range and a reliable quantification of 18F/68Ga-PSMA uptake using standard acquisition and reconstruction parameters within clinical PET/MRI protocols is possible. This allows for an individual assessment of potential therapy options for each patient.
To compare the diagnostic performance of ⁶⁸Ga-FAPI PET/CT, ¹⁸F-FDG PET/CT, and magnetic resonance imaging (MRI) in assessing primary tumor size, detecting additional intramammary foci, and identifying axillary lymph node metastasis (ALNM) in patients with invasive breast cancer (IBC) undergoing upfront surgery without neoadjuvant chemotherapy (NAC), using postoperative histopathology as the reference standard. This retrospective study included 60 IBC patients who underwent total mastectomy without NAC. All patients had preoperative ⁶⁸Ga-FAPI PET/CT, ¹⁸F-FDG PET/CT, and breast MRI. Primary tumor size, multifocality/multicentricity (MF/MC), and ALNM were evaluated for each modality. FAPI and FDG were additionally assessed for extra-axillary lymph nodes, internal mammary nodes, and distant metastases. Agreement between imaging- and pathology-based tumor size measurements, as well as the diagnostic performance for MF/MC and ALNM, were evaluated using correlation analyses and standard diagnostic accuracy metrics. MRI (ρ = 0.866) and ⁶⁸Ga-FAPI PET/CT (ρ = 0.844) demonstrated the strongest correlation with pathologic tumor size, whereas ¹⁸F-FDG PET/CT showed lower agreement (ρ = 0.780). Breast MRI (45.0%) and ⁶⁸Ga-FAPI-PET/CT (38.3%) were significantly superior to ¹⁸F-FDG PET/CT (18.3%) in detecting multifocal or multicentric disease (p < 0.001). For ALNM detection, breast MRI achieved the highest sensitivity (87.5%) but showed lower specificity (72.7%). In contrast, ⁶⁸Ga-FAPI PET/CT combined high sensitivity (81.2%) with perfect specificity (100.0%), outperforming ¹⁸F-FDG PET/CT, which demonstrated lower sensitivity (43.8%) despite high specificity (93.2%). Additionally, ⁶⁸Ga-FAPIPET/CT identified metastatic findings not detected by ¹⁸F-FDG PET/CT, including seven axillary lymph nodes (11.7%), 29 additional intramammary tumor foci (48.3%), and four distant metastases (6.7%). ⁶⁸Ga-FAPI PET/CT demonstrated higher diagnostic performance than ¹⁸F-FDG PET/CT and accuracy comparable to breast MRI for primary tumor size estimation and detection of multifocal or multicentric disease. FAPI-PET/CT also provided higher specificity than MRI for ALNM assessment and identified additional metastatic lesions not detected by FDG-PET/CT, supporting its potential role as a complementary modality to MRI and an alternative functional imaging technique in selected patients.
The aim of this retrospective study was to investigate whether gallium-68-labeled fibroblast activation protein inhibitor (⁶⁸Ga-FAPI) positron emission tomography/computed tomography (PET/CT) that provided altered staging and adjusted treatment decisions was more effective for prolonging patient survival compared to that achieved by either contrast-enhanced computed tomography (CE-CT) or fluorine-18-fluorodeoxyglucose (¹⁸F-FDG) PET/CT. We analyzed patients diagnosed with untreated gastric or colorectal cancer between March 2021 and March 2023 who were staged using these three imaging diagnostic modes described above. The accuracy of staging, reduction of unnecessary surgery, progression-free survival (PFS), and overall survival (OS) were used as the main comparative indicators. The potential independent risk factors affecting the prognosis of patients with gastric or colorectal cancer were also analyzed. A total of 270 patients (137 gastric and 133 colorectal cancers) were enrolled, with a median follow-up of 3.02 years (95%CI: 2.7-3.3 years). The baseline characteristics of the patient groups were comparable. For both cancers, patients staged by ⁶⁸Ga-FAPI PET/CT had significantly longer median OS than those staged by either CE-CT or ¹⁸F-FDG PET/CT (colorectal cancer: p = 0.0123; gastric cancer: p = 0.037). ⁶⁸Ga-FAPI PET/CT also improved the accuracy of staging and altered staging in 41%-52% of patients, with a reduction in unnecessary surgeries of 42%-69%. Cox multivariate regression identified CE-CT and ¹⁸F-FDG PET/CT as prognostic risk factors relative to ⁶⁸Ga-FAPI PET/CT. In patients with gastric or colorectal cancer, those who underwent staging with 68Ga‑FAPI PET/CT showed improvements in disease progression and survival outcomes compared with those staged with either CE‑CT or 18F‑FDG PET/CT. The underlying mechanisms of these improvements may be related to increased staging accuracy and the subsequent selection of less invasive therapeutic strategies. These findings highlight the clinical value of 68Ga‑FAPI PET/CT in these patient populations. (Trial registration: ChiCTR ChiCTR2400081233. Registered 27 February 2024).
Glioblastoma multiforme (GBM) remains an aggressive brain malignancy with dismal prognosis despite current standard-of-care therapies. The gastrin-releasing peptide receptor (GRPR) is overexpressed in gliomas and represents a potential therapeutic target. However, systemic radionuclide delivery is limited by poor tumor penetration and off-target toxicity. GRPR expression and prognostic relevance were analyzed using Chinese Glioma Genome Atlas and a clinical-trial dataset, respectively at the transcriptomic and protein levels. [177Lu]Lu-RM26, a lutetium-177-labeled GRPR-targeting antagonist, was evaluated in vitro, and administered intratumorally via convection-enhanced delivery in an orthotopic GL261Fluc+ glioblastoma model. Pharmacokinetic characteristics, including tumor retention and biodistribution, were evaluated by serial single-photon emission computed tomography and gamma-counting. Efficacy was assessed by tumor volume, bioluminescence signal, and overall survival. Safety was evaluated through body weight monitoring, neurological scoring, rotarod testing, hematology, and immunohistochemical staining. Mechanistic insights were obtained via bulk RNA-sequencing and Western blotting. Higher GRPR expression correlated with poorer-prognosis glioma subtypes and reduced survival. In vitro assays showed dose-dependent inhibition of GL261Fluc+ cell viability, proliferation, and invasion. Locoregional [177Lu]Lu-RM26 administration led to prolonged tumor retention (74.7 h), high absorbed dose (2.71 × 106 mGy·MBq- 1), and minimal off-target uptake. Treated mice exhibited marked tumor growth inhibition, reduced bioluminescence signal, and extended survival compared to controls. No significant short-term systemic toxicity or neurological impairment was observed. Transcriptome and Western blotting findings were consistent with DNA replication stalling and G2/M arrest. Locoregional [177Lu]Lu-RM26 therapy enables sustained, tumor-specific β-radiation with minimal systemic exposure, representing a promising locoregional strategy for GRPR-positive GBM.
The REASURE study investigated imaging biomarkers in men receiving 223Ra treatment for prostate cancer bone metastases. We used REASURE data to compare and contrast the roles of [18F]NaF PET/CT measurements of maximum standardised uptake value (SUVmax) and bone metabolic flux (Ki) as markers of response. Thirty-four men with prostatic bone metastases received up to six cycles of 223Ra (55 or 88 kBq/kg) at four-weekly intervals. Whole-body diffusion-weighted MRI and [18F]NaF PET/CT images were acquired at baseline and 4, 12, and 24 weeks later. Values of the apparent diffusion coefficient (ADC, a measure of tumour response), SUVmax, and a novel surrogate measurement of Ki using a PET/CT SUV measurement in the left ventricle were monitored in up to 5 bone metastases in each participant. Multilinear regression analysis (MLR) was performed to determine if changes in ADC were predicted by changes in SUVmax or Ki. Radium dose and baseline SUVmax were additional independent variables. ADC values increased throughout the study, while SUVmax and Ki decreased. MLR analysis showed that baseline SUVmax and 223Ra dose predicted ADC response (P < 0.001 and P < 0.01, respectively). Changes in SUVmax and Ki at 4, 12, and 24 weeks failed to predict the changes in ADC, showing decoupling between MRI and PET/CT measurements as markers of response. Changes in Ki were a highly significant predictor of changes in SUVmax (P < 0.001), reflecting the strong correlation between these two measurements. Baseline SUVmax was the best predictor of ADC response, followed by 223Ra dose. Changes in SUVmax and Ki failed to predict changes in ADC, suggesting that the changes in the PET/CT variables reflected the effect of 223Ra uptake on osteoblasts rather than a tumoricidal effect. A decrease in SUVmax seen on post-therapy [18F]NaF PET/CT scans should not be interpreted as evidence of tumour regression. ISRCTN ISRCTN17805587. Registered 21/01/15.
To evaluate the potential value of [18F]F-FAPI PET/CT for detecting inguinal lymph node (ILN) metastases in locally advanced penile squamous cell carcinoma (PSCC) and to compare the results with those of [18F]F-FDG PET/CT. In this prospective pilot study, 25 patients with histologically confirmed PSCC underwent both [18F]F-FAPI and [18F]F-FDG PET/CT followed by radical ILN dissection within 30 days. Diagnostic performance was assessed using postoperative histopathology as the reference. Semi-quantitative parameters (SUVmax, SUVmean, tumor-to-background ratio (TBR)) were analyzed, and immunohistochemical staining for FAP and GLUT1 was performed on resected lymph nodes to assess correlations with PET-derived metrics. Among 25 evaluable patients, 12 (48%) had pathologically confirmed lymph node metastases. On a patient-based analysis showed [18F]F-FAPI PET/CT achieved 100% accuracy in N-staging, compared to 72% for [18F]F-FDG PET/CT. On a lesion-based analysis, a total of 447 lymph nodes were dissected, of which 27 were confirmed as metastases. The sensitivity, specificity, positive predictive value, and accuracy for [18F]F-FDG vs. [18F]F-FAPI PET/CT were as follows: sensitivity, 0.89 (95% CI: 0.71-0.97) vs. 0.96 (95% CI: 0.81-1.00); specificity, 0.93 (95% CI: 0.90-0.95) vs. 1.00 (95% CI: 0.99-1.00); PPV, 0.44 (95% CI: 0.35-0.53) vs. 1.00 (95%CI: 0.87-1.00); and accuracy, 92.2% vs. 99.8%, respectively. Metastatic lymph nodes exhibited significantly higher SUVmax, SUVmean, and TBR than benign nodes, with [18F]F-FAPI demonstrating superior discriminative ability. Immunohistochemical analysis revealed markedly elevated expression of both FAP and GLUT1 in metastatic nodes than in benign nodes, with FAP upregulation being more pronounced. FAPI uptake correlated positively with FAP expression, whereas FDG uptake correlated positively with GLUT1 expression. [18F]F-FAPI PET/CT demonstrates promising diagnostic performance in detecting ILN metastases in patients with PSCC compared to [18F]F-FDG. This modality holds potential value in refining patient selection for inguinal lymph node dissection and reducing unnecessary surgical morbidity. ChiCTR2400085605. https://www.chictr.org.cn .
To investigate whether distinct patterns of cortical involvement exist in Parkinson's disease (PD) and to characterize their potential progression trajectories using multimodal neuroimaging and data-driven disease progression modeling. In this cross-sectional multimodal imaging study, we enrolled 317 patients with clinically diagnosed PD and 61 healthy controls. All participants underwent simultaneous FDG-PET and MRI scanning. We applied the Subtype and Stage Inference (SuStaIn) model to cortical glucose metabolism and thickness data to identify latent disease progression patterns. Network-level characteristics were further examined within a whole-brain gradient framework. Robustness was assessed through age- and sex-balanced sensitivity analyses in the local cohort and external validation using harmonized T1-weighted MRI data from the Parkinson's Progression Markers Initiative (PPMI) dataset. Two distinct cortical involvement subtypes were identified. One subtype showed predominant alterations in higher-order association networks, including the default mode and frontoparietal networks, whereas the other was characterized by greater involvement of lower-order sensorimotor and limbic systems. These subtype patterns remained stable across sensitivity analyses and external validation. Disease duration showed a significant correlation with the inferred disease stage (r = 0.15, p = 0.01). Imaging findings further revealed hypermetabolism in brainstem and trans-entorhinal regions accompanied by widespread cortical hypometabolism. Our findings reveal two robust cortical progression patterns in PD, highlighting substantial heterogeneity in network-level metabolic and structural involvement. This framework provides new insights into PD phenotypic variability and may support future efforts toward disease stratification and personalized research.
Ephrin type-A receptor 2 (EphA2) is a promising target in pancreatic ductal adenocarcinoma (PDAC). However, the clinical potential of targeting EphA2 requires further imaging evaluation. This study developed and preliminarily evaluated a novel 68Ga-labeled radiotracer for PET imaging of EphA2 expression in PDAC patients. 68Ga-FZEAR-1, 68Ga-FZEAR-2, and 68Ga-FZEAR-3 were synthesized, and their stability, affinity, pharmacokinetics were evaluated in vitro and in vivo. Further biological evaluation was performed in EphA2-positive and EphA2-negative tumor xenografts. A pilot first-in-human PET/CT study of the lead candidate, 68Ga-FZEAR-2, was subsequently conducted in two PDAC patients. The three 68Ga-radiotracers were synthesized with high radiochemical purity (> 99%) and demonstrated high stability and nanomolar affinity for EphA2. Cellular uptake was consistent with EphA2 expression and blocking assays confirmed specificity. In vivo, all tracers exhibited high tumor accumulation with low off-target uptake. 68Ga-FZEAR-2 showed favorable tumor-targeting ability, pharmacokinetics, and safety profile. In the pilot clinical study (n = 2), 68Ga-FZEAR-2 PET/CT visualized primary and metastatic lesions clearly without adverse effects. Immunohistochemical analysis confirmed EphA2 expression in lesions exhibiting high tracer uptake. A series of 68Ga-labeled tracers for EphA2 imaging was successfully developed and evaluated. The lead candidate, 68Ga-FZEAR-2, showed promising targeting specificity and favorable pharmacokinetics. A pilot study indicated that 68Ga-FZEAR-2 provided preliminary evidence of noninvasive visualization of EphA2 expression in PDAC patients, thereby suggesting its potential as a tool for precision diagnosis in PDAC.