[18F]BIBD-181 is a positron emission tomography tracer targeting synaptic vesicle glycoprotein 2A (SV2A), a molecular marker of synaptic density. This study aimed to establish an automated production method for [18F]BIBD-181 on the CFN-MPS200 platform and to evaluate its production consistency, radiochemical stability, and principal quality attributes. No-carrier-added [18F]fluoride was used for nucleophilic radiofluorination of precursor 6a. Reaction times of 10, 12, and 15 min were evaluated at 95 °C, and semipreparative HPLC purification was explored using acetonitrile/water ratios of 1:1, 2:3, and 3:7 (v/v), each containing 0.5% acetic acid. Radiofluorination for 12 min using 1.0 mg of precursor, followed by purification with acetonitrile/water (2:3, v/v) at 2.0 mL/min, provided the most favorable overall performance. Under the selected conditions, six independent automated production runs were completed in 74.80 ± 2.75 min, affording a non-decay-corrected radiochemical yield of 10.42 ± 0.57% and a radiochemical purity of 97.74 ± 0.76%. The final product was colorless and clear, with a pH of 7.15 ± 0.19. Analytical HPLC confirmed the chromatographic identity of [18F]BIBD-181, with a relative retention time of 1.03 compared with the nonradioactive [19F]BIBD-181 reference standard. Radiochemical purity remained above the predefined acceptance criterion of 90% for at least 240 min at room temperature. GC-FID analysis determined an ethanol content of 7.61% (v/v) and a residual acetonitrile concentration of 407.6 ppm. All three bacterial endotoxin assays met their corresponding predefined acceptance criteria and assay-suitability requirements. These findings demonstrate that [18F]BIBD-181 can be reproducibly prepared using an integrated automated workflow with high radiochemical purity and satisfactory short-term stability. The established procedure provides a practical radiochemical basis for routine tracer preparation and further preclinical and translational evaluation of [18F]BIBD-181 for SV2A PET imaging.

This study developed a novel 18F-labeled PET tracer, [18F]AromataPET-1, based on the aromatase inhibitor BIBD-071, with the core goal of achieving specific in vivo imaging of aromatase in both central...

Objectives:Accumulating studies have reported that some mild cognitive impairment (MCI) patients without significant β-amyloid (Aβ) deposition on amyloid positron emission tomography (PET) can later develop Alzheimer's disease (AD). Therefore, this study profiled the cognitive and neural characteristics of MCI patients with negative Aβ deposition to better understand potential features associated with an increased risk of AD progression. Methods:Thirty-seven MCI patients and 32 normal controls (NCs) underwent neuropsychological assessments, structural magnetic resonance imaging, and diffusion tensor imaging scans. MCI patients were stratified into amyloid-positive (Aβpos; n = 18) and amyloid-negative (Aβneg; n = 19) groups based on 18F-florbetapir PET. We compared cognitive performance, white matter (WM) integrity, and gray matter volume (GMV) across the three groups and further examined the interplay among brain structural alterations and cognitive changes. Results:Cognitively, relative to NCs, participants in Aβneg MCI group showed significant deficits in multiple cognitive domains including episodic memory, attention, and executive function, as those in Aβpos MCI group did. Both MCI subgroups exhibited extensive disruptions of WM integrity. Direct comparisons between the Aβneg and Aβpos groups revealed that Aβ-related structural changes were predominantly localized to the left hippocampus and adjacent regions. The increased Aβ deposition was closely associated with elevated mean diffusivity in the left hippocampal portion of the cingulum and reduced GMV of the left hippocampus. Moreover, the GMV of hippocampus could mediate the impact of WM disruption on episodic memory performance. Conclusion:Aβneg MCI patients who exhibit AD-like cognitive and structural abnormalities, particularly involving the hippocampus, may be associated with advanced cognitive decline or dementia progression. These results may help identify high-risk individuals within the heterogeneous Aβneg MCI population.

This study developed a novel 18F-labeled PET tracer, [18F]AromataPET-1, based on the aromatase inhibitor [18F]BIBD-071, with the core goal of achieving specific in vivo imaging of aromatase in both the central nervous system and peripheral tissues, providing a tool for related disease research and clinical diagnosis. [18F]AromataPET-1 demonstrated high affinity, specific uptake in aromatase-rich tissues like the stomach and ovaries in rats, and excellent blood-brain barrier penetration, enabling brain imaging. It also showed specific tumor visualization in MCF-7 xenograft mouse models, whose uptake could be blocked by letrozole. Potential species-dependent differences in aromatase expression between mice and rats were suggested. [18F]AromataPET-1 is a promising tool for studying aromatase in peripheral tissues and for companion diagnostics in breast cancer.

Purpose The present study aims to evaluate the value of whole-body 18 F-FDG PET/CT in distinguishing among different cerebellar tumor types. Methods We retrospectively analyzed 18 F-FDG PET/CT images of 86 patients with histologically confirmed cerebellar tumors, including 25 metastases, 17 lymphomas, 9 low-grade gliomas, 13 high-grade gliomas, 16 hemangioblastomas, and 6 medulloblastomas. Tumors were initially classified as PET-positive or PET-negative by visual assessment. For PET-positive cases, semiquantitative parameters—including the maximum, mean, and peak tumor-to-normal-brain ratios (TNRmax, TNRmean, and TNRpeak, respectively), metabolic tumor volume (MTV), and total lesion glycolysis (TLG)—were measured and compared pairwise. Parameters significant for differential diagnosis were evaluated using the area under the receiver operating characteristic curve (AUC) and accuracy. Additionally, the detection of suspicious extracranial malignancy on torso PET/CT was recorded, and its diagnostic value for metastasis was assessed. Results Nearly all hemangioblastomas were PET-negative, with visual assessment achieving a diagnostic accuracy of 97.67% for this tumor type. Lymphomas presented the highest TNRmax, TNRmean, and TNRpeak values, whereas low-grade gliomas presented the lowest values. For distinguishing lymphoma, the AUCs for TNRmax, TNRmean, and TNRpeak were 0.881, 0.889, and 0.898, respectively. When optimal cutoff values of > 1.67, > 0.94, and > 1.37 were used, the diagnostic accuracies were 71.01%, 75.36%, and 85.51%, respectively. For identifying low-grade glioma, the same parameters yielded AUCs of 0.904, 0.916, and 0.869, respectively. With optimal cutoff values of < 0.77, < 0.52, and < 0.62, the accuracies were 92.75%, 91.30%, and 89.86%, respectively. Medulloblastoma demonstrated the highest MTV and TLG. MTV yielded an AUC of 0.847 for differentiating medulloblastoma from other cerebellar tumors, and an optimal cutoff value of > 12.85 provided an accuracy of 89.86%. Torso PET/CT for detecting suspicious extracranial malignancy excelled at diagnosing metastasis, with an accuracy of 96.51%. Conclusion Visual analysis and metabolic parameters from brain 18 F-FDG PET are valuable for differentiating hemangioblastoma, lymphoma, low-grade glioma, and medulloblastoma. Whole-body PET/CT contributes to the diagnosis of metastasis by identifying suspicious extracranial malignancies.

BACKGROUND:The aim was to develop an attention-based model using 18F-fluorodeoxyglucose (18F-FDG) PET imaging to differentiate autoimmune encephalitis (AE) patients from controls and to discriminate among different AE subtypes. METHODS:This multi-center retrospective study enrolled 390 participants: 222 definite AE patients (comprising four subtypes: LGI1-AE, NMDAR-AE, GABAB-AE, GAD65-AE), 122 age- and sex-matched healthy controls, and 33 age- and sex-matched antibody-negative AE patients along with 13 age- and sex-matched viral encephalitis patients, both serving as disease controls. An attention-based multi-instance learning (MIL) model was trained using data from one hospital and underwent external validation with data from other institutions. Additionally, a multi-modal MIL (m-MIL) model integrating imaging features, age, and sex parameters was evaluated alongside logistic regression (LR) and random forest (RF) models for comparative analysis. RESULTS:The attention-based m-MIL model outperformed classical algorithms (LR, RF) and single-modal MIL in AE vs. all controls binary classification, achieving the highest accuracy (84.00% internal, 67.38% external) and sensitivity (90.91% internal, 71.19% external). For multiclass AE subtype classification, the MIL-based model achieved 95.05% (internal) and 77.97% (external) accuracy. Heatmap analysis revealed that NMDAR-AE involved broader brain regions, including the medial temporal lobe (MTL) and basal ganglia (BG), whereas LGI1-AE and GABAB-AE showed focal attention on the MTL and BG. In contrast, GAD65-AE demonstrated concentrated attention exclusively in the MTL. CONCLUSION:The m-MIL model effectively discriminates AE patients from controls and enables subtyping of different AE subtypes, offering a valuable diagnostic tool for the clinical assessment and classification of AE.

Background/Objectives: Aromatase plays a crucial role in the conversion of androgens to oestrogens and is often overexpressed in hormone-dependent tumours, particularly breast cancer. [18F]BIBD-071, which has excellent binding affinity for aromatase and good pharmacokinetics, has potential for the diagnosis and treatment of aromatase-related diseases. The MCF-7 cell line, which is hormone receptor-positive (HR+), was used in the assessment of the novel [18F]-labelled radiotracer [18F]BIBD-071 via positron emission tomography (PET) imaging of an HR+ breast cancer xenograft model. Methods: [18F]BIBD-071 was synthesised, radiolabelled, and then subjected to in vitro stability testing. MCF-7 cells were cultured and implanted into BALB/c nude mice to establish subcutaneous tumour models. MicroPET/CT imaging was conducted after injection of the tracer at 1 and 2 h, and a blocking study was also conducted using the aromatase inhibitor letrozole. A block experiment was used to prove the specificity of the probe. Biodistribution studies were performed at 0.5, 1, and 2 h post injection (p.i.). Immunofluorescence was used to assess aromatase expression in MCF-7 cells. Results: [18F]BIBD-071 showed excellent in vitro stability and specific uptake in an MCF-7 xenograft tumour model. MicroPET/CT imaging at 1 and 2 h p.i. revealed excellent tumour visualisation with a favourable tumour-to-background ratio. Biodistribution data revealed high tracer uptake in the liver, small intestine, and stomach, with significant washout from the bloodstream and tumour over time. The tumour uptakes at 0.5 h, 1 h, and 2 h were 3.84 ± 0.13, 2.5 ± 0.17, and 2.54 ± 0.32, respectively. The tumour uptake significantly decreased between 0.5 h and 1 h (p < 0.0001), whereas there was no significant difference between 1 and 2 h. The tumour/background ratios at 0.5 h, 1 h, and 2 h were 1.19 ± 0.03, 1.12 ± 0.17, and 1.42 ± 0.11, respectively. Immunofluorescence confirmed robust aromatase expression in MCF-7 cells, which was correlated with [18F]BIBD-071 tumour uptake. Conclusions: [18F]BIBD-071 is a promising PET tracer for diagnosing and monitoring HR+ breast cancer, warranting further research into hormone-dependent cancers.

Cancer neuroscience has implicated peritumoral neurons in facilitating breast-to-brain metastasis (BrBM) progression via the N-methyl-D-aspartate receptor (NMDAR), a glutamate (Glu) receptor. The Glu-glutamine (Gln) cycle converts Glu into Gln, forming the combined Glx pool. This study investigated the spatial distribution of phosphorylated GluN2B (pGluN2B), an NMDAR subunit, and Glx in BrBM. Ex vivo analysis revealed elevated pGluN2B expression in BrBM, particularly in tumor cores, while Glx levels were paradoxically reduced. In mouse models, glutamine-based positron emission tomography (Gln-PET) imaging revealed higher tracer uptake in BrBM than that in paired breast tumors, with uptake values correlated positively with Glx concentration and pGluN2B expression. Strong Gln-PET uptake in BrBM noninvasively indicated elevated Glx metabolism in a BrBM patient, confirmed by ex vivo staining. This study highlighted the regional distribution of NMDAR and Glx, underscoring their potential as diagnostic biomarkers for BrBM. Glutamine-based molecular imaging can noninvasively visualize the tumor microenvironment relevant to cancer neuroscience.

Accurate determination of H3 K27M mutation status is critical for prognosis evaluation and treatment planning in brainstem gliomas (BSGs). We developed a clinical-radiomics model integrating 11C-methionine (11C-MET) positron emission tomography (PET), magnetic resonance imaging (MRI), and clinical features for non-invasive, preoperative prediction of H3 K27M mutation status in BSGs. This retrospective study included 77 patients with newly diagnosed BSG who underwent preoperative 11C-MET PET imaging and MRI. Among them, 53 had a histologically confirmed H3 K27M mutation. Patients were randomly divided into training (n = 55) and test (n = 22) cohorts. Clinical variables significantly associated with H3 K27M mutation status were used to construct a clinical model using the ‌extreme gradient boosting ‌(XGBoost) algorithm. Radiomics features were extracted separately from PET and MRI images to construct individual and combined models. A clinical-radiomics integrated model was then developed by combining clinical features and the radiomics model with the best predictive performance. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC), calibration curve, and decision curve analysis (DCA). The clinical model achieved AUCs of 0.795 and 0.790 in the training and test cohorts, respectively. The combined PET-MRI radiomics model outperformed individual PET or MRI model, with AUCs of 0.876 and 0.848 in the training and test cohorts, respectively. The clinical-radiomics integrated model achieved the highest performance with AUCs of 0.886 in the training cohort and 0.876 in the test cohort. The calibration curve showed good agreement between predicted and actual outcomes, and DCA demonstrated a superior net clinical benefit of the integrated model. Radiomics analysis based on 11C-MET PET and MRI can effectively predict H3 K27M mutation status in BSGs. Incorporating clinical features further enhances predictive performance, supporting its use in non-invasive, preoperative molecular diagnosis. Not applicable.

The metabolic signature of anti-leucine-rich glioma-inactivated 1 (anti-LGI1) autoimmune encephalitis remains poorly defined. We sought to delineate disease-specific 18F-FDG PET patterns and assess their relationships with clinical severity and cognition. Forty-seven patients with anti-LGI1 encephalitis and 25 healthy controls underwent 18F-FDG PET/CT, and voxel-wise comprised to identify regional metabolic alterations. A disease-specific metabolic pattern was derived with fivefold cross-validation, and a metabolic covariance network was mapped using the Brainnetome atlas. Pattern expression scores were correlated with clinical assessments. Compared to controls, patients demonstrated hypermetabolism in the hippocampal rostal, nucleus accumbens (NAc), and hypothalamus, alongside hypometabolism in the dorsolateral prefrontal cortex and posterior cingulate cortex (PCC). We identified a robust metabolic pattern centered on the NAc with extensions to the hippocampus, prefrontal cortex, and PCC; expression of this pattern correlated positively with both clinical severity and cognitive impairment. Subgroup analyses showed no significant differences in basal ganglia metabolism between patients with and without faciobrachial dystonic seizures (FBDS), or in hypothalamic metabolism between those with and without hyponatremia. Overall, 18F-FDG PET uncovers a NAc-centered metabolic network that parallels disease severity in anti-LGI1 encephalitis. Our study offers potential biomarker for clinical evaluation and provides valuable insights into the underlying pathogenesis of clinical manifestations.

PurposeAccurate delineation of tumor margins and maximal safe resection are critical for successful curative oncologic surgery. However, fibroblast activation protein (FAP)-targeted probes suitable for fluorescence imaging remain limited. Here, we developed novel FAP-targeted fluorescent probes to accurately delineate tumor margins and enable rapid intraoperative identification of tumor boundaries in resected specimens.MethodsDOTA chelator for radiolabelling with gallium-68 was incorporated into dual-modality FAP-targeted probes synthesised by conjugating FAP-2286 and 3BP-3940 with the near-infrared (NIR) fluorophore IRDye800CW. These probes were evaluated both in vitro and in vivo using HEK293T-FAP cells stably expressing FAP and xenograft mouse models. Positron emission tomography (PET) and (NIR-II) fluorescence imaging assessed the specificity and ability of probes to delineate tumor margins. For clinical validation, resected lung tissue was incubated ex vivo with the probes. Tumor regions and margins were identified using fluorescence imaging and subsequently validated by haematoxylin and eosin (H&E) staining and FAP immunohistochemistry.ResultsBoth IRDye800CW-FAP-2286 and IRDye800CW-3BP-3940 exhibited high affinity for FAP-positive cells in vitro. PET imaging revealed high tumor specificity for both probes in vivo. In vivo and ex vivo NIR-II fluorescence imaging enabled accurate visualisation of tumor margins, with IRDye800CW-3BP-3940 exhibiting superior performance compared with IRDye800CW-FAP-2286. In the clinical specimen, IRDye800CW-3BP-3940 successfully delineated tumor regions with strong concordance to histopathological findings.ConclusionWe developed and validated a novel dual-modality molecular probe, IRDye800CW-3BP-3940, which integrated PET and NIR fluorescence imaging capabilities. This probe enabled highly specific detection of FAP-positive tumors and precise delineation of tumor margins in resected specimens.

PURPOSE:Anti-AMPAR encephalitis is a rare antibody-mediated disorder, and its clinicoradiological profile is incompletely defined. We aimed to characterize the clinical presentation and cerebral metabolic patterns of Chinese adults with anti-AMPAR encephalitis using 18F-FDG PET/CT. METHODS:From August 2016 to August 2022, we retrospectively identified patients from two neurology centers who were positive for anti-AMPAR antibodies in serum and/or cerebrospinal fluid. Demographic data, presenting symptoms, MRI and 18F-FDG PET/CT findings (Discovery Elite, GE Healthcare), treatment regimens, and outcomes were extracted and analyzed. RESULTS:Eight patients (four women) were included; median age was 53 years (range 37-63). Anti-AMPA2R antibodies were detected in seven cases and anti-AMPA1R antibodies in one. Limbic manifestations dominated, particularly cognitive decline and abnormal behavior; severe disease necessitated intensive care support in one patient, who nonetheless achieved a good outcome. Malignancy was documented in three individuals (lung carcinoma, hepatocellular carcinoma, and thymoma), and three harbored additional neural autoantibodies. MRI was abnormal in five patients (62.5%). All five subjects who underwent 18F-FDG PET/CT displayed prefrontal hypometabolism; three also showed posterior cingulate hypometabolism. Focal hypermetabolism was observed in the right temporal lobe (one case) and in the left thalamus (one case). CONCLUSION:Anti-AMPAR encephalitis usually presents as limbic encephalitis and is marked by prefrontal and posterior cingulate hypometabolism on 18F-FDG PET/CT. In some instances, hypermetabolism was observed in the basal ganglia or temporal lobes, possibly reflecting the local blood flow.

To verify its application potential in the field of cardiac and cerebral disease diagnosis, the first human experiment of [18F]BIBD-239 was reported. Synthesized via a GMP-compliant automated process on a CFN-MPS200 synthesizer (per Chinese Pharmacopoeia 2020), it achieved radiochemical purity >95%, nondecay-corrected yield >15%, and molar activity >120 GBq/μmol (total synthesis time 80 ± 5 min) under optimized conditions (95 °C, 10 min). Preclinical studies in rats confirmed TSPO-specific binding. First-in-human studies (6 healthy volunteers, 1 high-grade glioma (HGG), 1 low-grade glioma (LGG)) showed it rapidly crossed the blood-brain barrier with low normal brain retention and high sustained myocardial uptake without in vivo defluorination. HGG had higher tumor-to-background ratios (3.09) than LGG (2.33), with uptake beyond MRI-enhanced regions, correlating with histopathology. The whole-body effective dose (0.0145 ± 0.0018 mSv/MBq) was lower than [18F]FDG. [18F]BIBD-239 has robust synthesis, favorable pharmacokinetics, and TSPO-specific binding, enabling dual utility in noninvasive glioma grading and glucose-independent myocardial imaging, supporting translation in neuro-oncology and cardiovascular assessment.

Limbic hypermetabolism is a frequently observed manifestation of anti-LGI1 encephalitis on 18 F-FDG PET/CT imaging. In this case report, we present an atypical finding on 18 F-FDG PET/CT in a patient with anti-LGI1 encephalitis and negative MRI results. Apart from the expected hypermetabolism in the bilateral limbic system, there was also an uncommon intense uptake of 18 F-FDG noted in the bilateral frontoparietal cortex. Subsequent follow-up scans demonstrated normalized metabolism following treatment. The case highlights that neocortical hypermetabolism can be a characteristic feature of active anti-LGI1 encephalitis on 18 F-FDG PET/CT imaging.

To evaluate the characteristics of Aβ deposition in cognitive impairment patients with hallucinations. A retrospective analysis was performed on the AV45 PET imaging of 9 cognitive impairment patients with hallucinations (CI-H) and 9 cognitive impairment patients without hallucinations (CI-N). The data were analyzed using the cortexID suite. The whole cerebellum was selected as the reference brain region, and the SUVR of each cortical brain region was calculated. In the CI - H group, there were 5 males and 4 females, aged 59 - 88 years old, with a disease course of 1 - 7 years. In the CI - N group, there were 4 males and 5 females, aged 55 - 82 years old, with a disease course of 1 - 6 years. By visual assessment, 6 cases in the CI - H group had positive AV45 PET imaging and 3 cases were negative. In the CI-N group, 7 cases were positive and 2 cases were negative. The SUVR of the composite cortex in the CI-H group was 1.23±0.23, and that in the CI-N group was 1.23±0.24. In the CI-H group, 6/9 cases (66.7%) had the highest radiotracer uptake in the occipital cortex (left/right: 5/1), while in the CI-N group, only 2/9 cases (22.2%) had the highest radiotracer uptake in the occipital cortex. The former was more than the latter, but there was no significant statistical difference. In the CI-H group, 2 cases had the highest uptake in the left precuneus and posterior cingulate gyrus, and 1 case had the highest uptake in the left lateral temporal cortex. In the CI - N group, 5 cases had the highest uptake in the precuneus and posterior cingulate gyrus (4 cases on left and 1 case on right ), and 2 cases had the highest uptake in the left anterior cingulate gyrus. The SUVR of the occipital lobe in the CI-H group (L:1.39±0.24 and R:1.33±0.22 ) was higher than that in the CI - N group (L:1.34±0.24 and R:1.29±0.19 ), but there was no significant statistical difference. Aβ preferentially deposits in the left occipital cortex in cognitive impairment patients with hallucinations.

Fibroblast activation protein-α (FAP) has emerged as a promising target in the field of radiopharmaceuticals due to its selective expression in cancer-associated fibroblasts (CAFs) and other pathological conditions involving fibrosis and inflammation. Recent advancements have focused on developing FAP-specific radioligands for diagnostic imaging and targeted radionuclide therapy. This perspective summarized the latest progress in FAP radiopharmaceutical development, highlighting novel radioligands, preclinical evaluations, and potential clinical applications. Additionally, we analyzed the advantages and existing problems of targeted FAP radiopharmaceuticals, and discussed the key breakthrough directions of this target, so as to improve the development and conversion of FAP-targeted radiopharmaceuticals.

Background Breast cancer (BC) is currently the most common malignancy worldwide and the leading cause of cancer-related death in women. Positron emission tomography/computed tomography (PET/CT) with fluorine-18-2-fluoro-2-deoxy-glucose (18F-FDG-PET) plays an important role in staging breast cancer and now many promising tracers for tumor imaging are striving for superior breast cancer detection and monitoring. Some studies have reported better results regarding the diagnostic and therapeutic value of FAP ligands, especially in the diagnostic evaluation of primary BC. Methods In this study, we have successfully radiolabeled the 68Ga-OncoFAP which is FAP (Fibroblast activation protein) targeting tracer, and tested the imaging efficacy in both subcutaneous ER-positive MCF-7 breast cancer tumors models and orthotopic triplenegative MDA-MB-231 breast cancer tumor models. Results MCF-7 subcutaneous tumors and MDA-MB-231 orthotopic tumors exhibited high uptake of 68Ga-OncoFAP, which correlated with the corresponding pathological results. Between 30 and 100min post injection, the tumor-to-background ratio (TBR) of MDA-MB-231 orthotopic tumors gradually decreased, but to a limited extent, all less than 10%. 68Ga-labeled OncoFAP could be applied for noninvasive imaging of breast cancer and we could observe the metabolism of the probe by the MicroPET imaging. Conclusions 68Ga-OncoFAP could selectively image fibroblast activation protein in mice models and is very promising for the diagnosis of different histological and molecular subtypes of breast cancer.