Design, synthesis, and characterization of F-18 sigma-1 receptor radiotracers for Alzheimer disease.

Pre-operative imaging in clinical International Federation of Gynecology and Obstetrics stage IB2 or less cervical carcinoma.

This study aimed to investigate whether there are metabolic connectivity alterations in the brain of rats with a depressive-like phenotype, using positron emission tomography (PET) and graph theory methods. Male Wistar rats were exposed to 5 days of repeated social defeat (RSD) to induce a depressive-like phenotype, and brain connectivity was assessed with [18F]FDG-PET. Sucrose preference tests were conducted to assess anhedonia-like behaviour, a symptom of depression. The results showed that anhedonia-like behaviour was present one day after RSD and recovered after seven days. The analysis of large-scale brain networks revealed a reduction in connectivity in the default mode network of RSD-exposed animals one day after RSD, suggesting a link between reduced connectivity and the presence of anhedonia-like behaviour. Seven days after RSD, an increase in connectivity was observed in the salience network, which coincided with the recovery of sucrose preference. Modular analysis revealed different configurations of brain regions at one and seven days after RSD, with asymmetrical segregation of left and right hemisphere structures. These findings suggest that changes in brain connectivity may play a role in the development and recovery of anhedonia-like behaviour in rats exposed to RSD and may have implications for understanding depressive phenotypes.

SCN2A gene mutations, which affect the function of the voltage-gated sodium channel NaV1.2, are associated with a spectrum of neurological disorders, including epileptic encephalopathies and autism spectrum disorders. Advanced imaging modalities such as magnetic resonance imaging (MRI) and positron emission tomography (PET) have been instrumental in elucidating the neuroanatomic and functional alterations associated with these mutations.

Transcranial direct current stimulation (tDCS) is a clinically promising neuromodulatory therapy, capable of promoting function and motor recovery after stroke. Beyond the primary stroke lesion, remote networks disturbances, e.g., stroke-induced secondary neurodegeneration (SND), are related to long-term disabilities. Under the hypothesis that tDCS promotes recovery by supporting neuroprotection, we investigated the effects of tDCS on thalamic SND after stroke. Three days after cortical stroke, induced by photothrombosis, cathodal tDCS over the lesioned cortex was performed daily for ten days (39.6 kC/m2). SND, i.e., neuronal loss, and inflammation in the ipsilesional thalamus were evaluated ex vivo 28days after stroke. Parameters of functional thalamic network integration measured by resting-state functional magnetic resonance imaging (rs-fMRI) were conducted longitudinally. To assess the effects of tDCS on glucose metabolism, positron emission tomography (PET) was performed after a similar tDCS regimen in healthy mice. Repetitive tDCS decreased the ipsilateral thalamic glucose metabolism in unlesioned animals. Four weeks after cortical stroke, secondary glial scaring was found in the ipsilesional thalamus, its extent correlating to the cortical lesion size (R2=0.54, p<0.001). Notably, while it did not affect glial scaring, tDCS reduced thalamic neurodegeneration by over 60% (p<0.05), being reflected by parameters of functional thalamic integration as assessed by rs-fMRI. Additionally, tDCS downregulated the pro-inflammatory polarization of microglia. Overall, tDCS ameliorated the stroke-induced remote SND, in parallel to mitigating sustained neuroinflammation. Thus, the data show that tDCS exerts previously unknown effects on remote brain regions after stroke.

From permeability to prediction: evolving strategies for evaluating oral drug absorption.

Positron emission tomography (PET) using radiolabeled antibodies (radioimmunoconjugates) is a powerful imaging technique to track the distribution of therapeutic antibodies. Accurate determination of the average number of chelators per antibody (CAR) is essential for (radio)immunoconjugate characterization, which is important for maximizing tumor uptake and image quality. Determination of the CAR is considered a critical quality attribute. Radiometric titration, although widely used, is labor-intensive, material- and time-consuming, and requires approximately half a day per sample. To overcome this analytical bottleneck, we developed a microscale size exclusion chromatography - mass spectrometry (SEC-MS) analysis. By applying microscale flow, high concentrations of volatile salts, up to 1000mM ammonium acetate, could be used to minimize secondary interactions. Moreover, high isCID energy of 140eV was applied to reduce adduct formation and enhance the MS sensitivity. The method was optimized using model radioimmunoconjugates based on intact trastuzumab, with a particular focus on the impact of buffer concentration on both chromatographic effects and CAR determination. A final buffer concentration of 600mM ammonium acetate was selected. The method was compared with radionuclide titration for analysis of the same immunoconjugate model and yielded similar results. Finally, we demonstrated the broad applicability of the method by testing diverse immunoconjugates (e.g., ipilimumab, rituximab), including cysteine- and lysine-linked chelators (e.g., DFO, DOTA, RESCA), as well as other smaller protein models, such as nanobodies. The optimized microflow native SEC-MS method, with a rapid 20-min run time, provides comprehensive characterization, including determination of the average CAR, dispersity index, glycosylation profile, and mAb impurities. Crucially, this native approach is applicable to all tested immunoconjugates, including chemically sensitive species such as those with maleimide and thiourea linkages, which often challenge denaturing methods like RPLC-MS. This establishes SEC-MS as a broadly applicable alternative to radiometric titration for the comprehensive characterization of immunoconjugates.

The retinal nerve fiber layer mean thickness in patients with early Parkinson's disease reflects striatal dopamine function.

Anti-LGI-1 autoimmune encephalitis: Insights from literature and a very late-onset case report.

Therapeutic management of inflammatory heart diseases.

Prognostic value of 18F-fluorodeoxyglucose positron emission tomography one month after initiation of prednisolone therapy in patients with cardiac sarcoidosis.

Prostate cancer is the most frequently identified cancer in men and remains a major cause of cancer-related deaths. Precise and prompt diagnosis is crucial for differentiating clinically relevant tumours from non-aggressive lesions and for guiding treatment choices. Multiparametric magnetic resonance imaging (mp MRI) has transformed prostate cancer detection through accurate lesion localization, risk assessment, and enhanced biopsy targeting. Fusion biopsy, integrating mp MRI results with real-time transrectal ultrasonography (TRUS), has become a highly efficient technique for sampling concerning lesions. Over the past thirty years, there have been swift advancements in the diagnosis and treatment of prostate cancer, such as multiparametric magnetic resonance imaging, positron emission tomography, robotic surgery, image-guided hypo fractionated and stereotactic radiotherapy, new anti-androgens, and radioligand therapies. This review addresses the current management of every stage of prostate cancer in view of recent advancements, allowing for comprehensive personalization of treatment, and highlights the potential of future studies to enhance results even further. In this document, we provide an extensive overview of the evidence backing the use of chemotherapy in the current management of advanced prostate cancer, focusing particularly on the application of chemotherapy for aggressive variant prostate cancer (such as neuroendocrine prostate cancer) and the integration of chemotherapy with androgen signalling inhibitors. As prostate cancer research advances quickly, producing new agents and treatment methods, chemotherapy remains vital for extending the lives of patients with advanced and metastatic prostate cancer.

This study was undertaken to test whether arterial spin labeling (ASL) performs comparably to 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET), the mainstay functional imaging technique, in pediatric lesional epilepsy, while avoiding radiotracer exposure and additional sedation. We retrospectively included children with epilepsy due to focal cortical dysplasia, low-grade epilepsy-associated tumors, or hippocampal sclerosis who underwent standardized magnetic resonance imaging (MRI; including single-delay ASL) and FDG-PET during presurgical evaluation. Lesions, perilesional perfusion, and metabolic abnormalities were segmented and coregistered. Spatial overlap was quantified using DICE scores to compare functional modalities with each other (perfusion-to-metabolism: DICEP-to-M), with the lesion (metabolism-to-lesion: DICEM-to-L; perfusion-to-lesion: DICEP-to-L), and, in seizure-free children, with the resection cavity (lesion-, metabolism-, perfusion-to-resection cavity: DICEL-/M-/P-to-Post). We also assessed the temporal stability of perilesional ASL abnormalities and the presence of remote ipsilateral/contralateral abnormalities. Equivalence testing used the Wilcoxon signed-rank equivalence test with FDG-PET as reference; Cohen κ quantified agreement for remote abnormalities. Fifteen children were included; median ages at FDG-PET and ASL were 7.7 and 7.5 years; 53% required sedation. Median perilesional volumes were 11 339 mm3 (FDG-PET) and 10 791 mm3 (ASL); both were larger under sedation (p < .001). Perilesional volumes were equivalent (p = .037). Median DICEM-to-L and DICEP-to-L were .3 and .4; equivalence was confirmed (p < .001). Median DICEP-to-M was .7, indicating strong ASL-FDG-PET concordance. In seizure-free children following surgery, DICEM-to-Post and DICEP-to-Post were both .6 and equivalent (p = .01). ASL findings were stable over time (DICE = .27-.75; n = 4 with repeat ASL). Remote ipsilateral abnormalities were common (ASL 73%, FDG-PET 67%; κ = .53), with poor contralateral agreement (κ = .12). ASL yielded perilesional findings equivalent to FDG-PET and showed comparable overlap with the resection cavity in seizure-free children. As a radiation-free technique embedded into routine MRI, ASL reduces logistics and avoids an additional sedation session. These findings support ASL as a practical alternative to FDG-PET for presurgical workup, especially when FDG-PET access is limited.

Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST) quantifies changes in radiotracer uptake to assess therapeutic response in cancer. However, the accuracy of these quantifications depends on imaging parameters, tumor size, and the local tumor-to-background uptake ratio (local-TBR). In this study, 'background' refers to the surroundings of the lesion rather than a standardized reference tissue. A NEMA Image Quality phantom was filled with 18F-FDG at varying sphere-to-background ratios to simulate clinical scenarios corresponding to PERCIST-defined thresholds for partial metabolic response (-30%) and progressive metabolic disease (+30%). Positron emission tomography (PET)/computed tomography imaging revealed that measured uptake changes systematically underestimated the true ±30% differences, particularly in smaller spheres. These findings indicate a potential source of systematic error in PET-based tumor response assessment, which may influence clinical interpretation. Further studies are recommended to investigate the effects of varying imaging parameters, tumor types, and clinical settings to improve the robustness of PERCIST-based evaluations.

Human epidermal growth factor receptor 2 (HER2) is a critical therapeutic target in various cancers, but its accurate noninvasive quantification remains challenging. Existing positron emission tomography (PET) tracers, such as antibodies and peptides, are limited by suboptimal clearance, insufficient tumor uptake and retention, and poor proteolytic stability. Here, we introduce a new class of disulfide-directed multicyclic peptides (DDMPs) that combine a conformationally rigid and stable scaffold with excellent HER2-binding properties. Using yeast display and directed evolution, we identified optimized DDMPs with single-digit nanomolar affinity for HER2. Alanine scanning mutagenesis revealed conserved residues that were amenable to functional modification. After gallium-68 (68Ga) radiolabeling, these DDMPs demonstrated significantly enhanced tumor accumulation, prolonged retention, and superior sensitivity in detecting HER2-expressing tumors compared to those of existing peptide tracers. Our work establishes DDMPs as a structurally distinct class of peptide tracers with superior performance, representing a significant advancement toward the clinical translation of precision PET imaging for HER2-positive cancers.

The study investigates how sex and age influence treatment response in paediatric, adolescent and young adult (AYA) classical Hodgkin lymphoma (cHL), integrating clinical data, immune-gene profiling and metabolic imaging from the European Network for Paediatric Hodgkin Lymphoma (EuroNet-PHL-C2 trial). cHL patients treated in Italian Association of Pediatric Hematology & Oncology Research (AIEOP)centres (2018-2020) underwent fluorodeoxyglucose-positron emission tomography (FDG-PET) at baseline, after two chemotherapy cycles early response assessment (ERA) and post-chemotherapy (late response assessment, LRA). Responses were classified as early complete metabolic response (CMR) or as adequate response (AR), inadequate (IR) or progressive disease at LRA. Tumour samples were profiled for 730 immune-related genes, and clinical and quantitative positron emission tomography parameters were integrated to assess sex- and age-related patterns. Sixty-eight cases passed quality control. Early CMR occurred in 51.5% at ERA; 29.4% showed (AR) at LRA. Older age (≥13 years), especially in males, was associated with higher IR risk. runt-related transcription factor 3 (RUNX3) expression characterized CMR; a five-gene panel (Bone Marrow Stromal Cell Antigen-1/CD157 [BST1]; C-X-C Motif Chemokine Receptor 6 [CXCR6]; Inducible T-cell Co-stimulator/CD278 [ICOS], Ubiquitin Specific Peptidase 9 Y-Linked [USP9Y], and Single Ig IL-1-Related Receptor/IL-1R8 [SIGIRR]) predicted IR and reflected sex-related immune differences. USP9Y expression correlated with baseline tumour volume (total metabolic tumour volume, TMTV1). Combining TMTV1 with RUNX3 improved CMR discrimination, while TMTV1 with the five-gene panel increased sensitivity but reduced accuracy at LRA. Sex and age influence immune response in AYA cHL. RUNX3 and the five-gene panel show promise as biomarkers of early and late response.

Neuroinflammation, measured using [11C](R)-PK11195 positron emission tomography (PET), has been reported in isolated rapid-eye-movement sleep behavior disorder (iRBD), but its temporal progression is unknown. The aim was to assess longitudinal progression of neuroinflammation in iRBD patients and its relationship with phenoconversion into Parkinson's disease (PD) or dementia with Lewy bodies (DLB). Sixteen iRBD patients received longitudinal [11C](R)-PK11195 PET scans over 3 years and were followed up clinically for 8 years to record phenoconversion into PD and DLB. We found significant progression of neuroinflammation in the putamen among other regions, with a trend to cortical increase over 3 years. During the clinical follow-up, 7 patients converted, and subgroup analyses suggested that the converters differed in progression patterns, with PD converters exhibiting increases and DLB exhibiting decreases in inflammation. This exploratory study suggests that progression of neuroinflammation in iRBD patients depends on their clinical trajectories, and this could be impactful in immune-modifying treatments. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Cardiac sarcoidosis (CS) is a rare and complex disease that requires a multidisciplinary approach for diagnosis and treatment. The diagnosis of CS can be confirmed by histological examination of non-caseating granulomas in cardiac or extracardiac tissue, along with supportive clinical and imaging findings. Symptoms are often non-specific, and the yield of endomyocardial biopsy is low due to the patchy nature of cardiac involvement-thus, many cases are not straightforward to diagnose, especially when pulmonary or extracardiac features are absent. Modern non-invasive imaging modalities have unique strengths in assessing the myocardium's structure, function, perfusion, inflammation and fibrosis-abnormalities of all these features exist in CS in varying degrees and can be integrated to assist in the diagnosis. Echocardiography is universally used as the initial imaging test when CS is suspected and provides information on cardiac structure and function, but is limited by inadequate tissue characterisation and differentiation from other infiltrative or restrictive cardiomyopathies. Positron emission tomography (PET) and cardiovascular magnetic resonance (CMR) have good accuracy in diagnosing CS. With current tissue characterisation techniques, such as T1 and T2 parametric mapping, CMR imaging can detect subclinical or early CS. While CMR has better overall prognostic utility for arrhythmic risk and cardiac mortality, fluorodeoxyglucose (FDG)-PET is superior in monitoring disease activity and guiding anti-inflammatory therapy. Hybrid FDG-PET/CMR imaging is a newer, complementary approach that is being increasingly used in centres of excellence. It combines the unique strengths of both modalities, thereby achieving superior sensitivity and specificity.

Myocardial viability imaging plays a pivotal role in evaluating patients with ischemic cardiomyopathy who may benefit from revascularization. Despite recent trials questioning its prognostic value, imaging continues to shape therapeutic decisions. This comprehensive review explores the underlying pathophysiological basis, diagnostic modalities, and clinical evidence on myocardial viability. We compare contemporary imaging tools and outline a practical framework for individualized patient assessment. Advanced modalities such as cardiac magnetic resonance, positron emission tomography, and dobutamine stress echocardiography provide robust insights into myocardial viability. Findings from key clinical trials, including STICH and REVIVED-BCIS2, reveal the nuanced role of viability in guiding revascularization strategies. We propose that myocardial viability testing remains a valuable adjunct in selected clinical scenarios, emphasizing integration with ischemia assessment, anatomical context, and symptom burden.

Uterine fibroids are the most common benign tumors in women. The increasing incidence of uterine fibroids has led to their increasingly common occurrence in young patients who have not yet achieved reproductive function. This has also led to an increase in the number of cases of uterine leiomyosarcoma diagnosed after organ-preserving surgery for uterine fibroids. Improving the quality of diagnostic examinations for patients with uterine fibroids and, accordingly, improving preoperative diagnostic methods for uterine sarcoma have long been a pressing issue in gynecology. Unfortunately, it remains virtually impossible to distinguish between uterine fibroids and leiomyosarcoma preoperatively. Despite the rapid advancement of imaging techniques (magnetic resonance imaging, computed tomography, and positron emission tomography with computed tomography), suspecting a malignant tumor of the uterine body is rare. This article presents a clinical case of uterine leiomyosarcoma diagnosed in a 25-year-old patient who had not realized her reproductive function. Uterine fibroids were first diagnosed at age 21; despite radical surgical treatment, a relapse was diagnosed shortly thereafter. During a repeat surgical procedure, the uterine tumor was classified as low-grade leiomyosarcoma, necessitating radical treatment—hysterectomy—despite the patient’s young age. Leiomyosarcoma is characterized by an aggressive course and poor prognosis, as clearly demonstrated in the presented clinical case. Despite the fact that the patient underwent laparotomy with ablastic retrieval of macroscopic specimens, multiple tumor disseminations were detected within a short period of time (6 months) in the abdominal cavity, lungs, bones, and anterior abdominal wall. Combined drug therapy and surgical treatment of recurrent tumors allowed for successful treatment of the patient with multiple metastases from uterine leiomyosarcoma for 7 years. Despite the rare nature of uterine leiomyosarcoma, patients with uterine fibroids, even young patients, require oncological vigilance and close medical attention at all stages—from outpatient examination up to the choice of treatment strategy, the extent and approach of surgery, and postoperative follow-up.