Elevated FDG uptake in non-tumorous lung regions does not predict immune checkpoint inhibitor-related pneumonitis in lung cancer patients.

Background: Predictors for checkpoint inhibitor-related pneumonitis (cinrPneumonitis) are desperately needed. This study aimed to investigate the pretreatment standardized uptake value (SUV) on [F]FDG-PET/CT of non-tumorous lung tissue as a predictive imaging marker for the development of cinrPneumonitis in 239 patients with lung cancer.

Methods: All patients with lung cancer receiving [F]Fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) prior to immune checkpoint inhibitor (ICI) therapy were included and retrospectively analyzed.

Early intervention anti-Aβ immunotherapy attenuates microglial activation without inducing exhaustion at residual plaques.

Anti-amyloid β-peptide (Aβ) immunotherapy was developed to reduce amyloid plaque pathology and slow cognitive decline during progression of Alzheimer's disease. Efficient amyloid clearance has been proven in clinical trials testing anti-Aβ antibodies, by their impact on cognitive endpoints correlating with the extent of amyloid removal. However, treatment is associated with adverse side effects, such as oedema and haemorrhages, which are potentially linked to the induced immune response.

Connectivity as a universal predictor of tau progression in atypical Alzheimer's disease.

The link between regional tau load and clinical manifestation of Alzheimer's disease (AD) highlights the importance of characterizing spatial tau distribution across disease variants. In typical (memory-predominant) AD, the spatial progression of tau pathology mirrors the functional connections from temporal lobe epicenters. However, given the limited spatial heterogeneity of tau in typical AD, atypical (non-amnestic-predominant) AD variants with distinct tau patterns provide a key opportunity to investigate the universality of connectivity as a scaffold for tau progression.

Early Locus Coeruleus noradrenergic axon loss drives olfactory dysfunction in Alzheimer's disease.

Alzheimer's disease (AD) often begins with non-cognitive symptoms such as olfactory deficits, which can predict later cognitive decline, though the mechanisms remain unclear. Pathologically, the brainstem locus coeruleus (LC), the main source of the neurotransmitter noradrenalin (NA) modulating olfactory information processing is affected early. Here we show early and distinct loss of noradrenergic input to the olfactory bulb (OB) coinciding with impaired olfaction in an AD mouse model, before appearance of amyloid plaques.

Co-occurrence of multiple pathologies in a case of frontotemporal dementia with TBK1 mutation: first in vivo detection of alpha-synuclein and tau co-pathology.

We present the case of a 74-year-old woman with behavioral variant frontotemporal dementia (bvFTD) linked to a pathogenic TANK-binding kinase 1 (TBK1) mutation (c.1349_1352del; p.Ile450Lysfs*15).

Design, Synthesis and Preclinical Evaluation of a Brain-Permeable PET Tracer for P2Y12 Receptor Imaging in the Brain.

Microglia, the innate immune cells of the central nervous system (CNS), act as first responders to brain injury. Their ability to switch between different neuroprotective and neurotoxic phenotypes, plays a central role in maintaining brain homeostasis. Recently, the P2Y12 receptor (P2Y12R) has been identified as a promising molecular biomarker for microglia activity, as its expression level is dependent on microglia phenotype and function.

Tau PET positivity in individuals with and without cognitive impairment varies with age, amyloid-β status, APOE genotype and sex.

Tau positron emission tomography (PET) imaging allows in vivo detection of tau proteinopathy in Alzheimer's disease, which is associated with neurodegeneration and cognitive decline. Understanding how demographic, clinical and genetic factors relate to tau PET positivity will facilitate its use for clinical practice and research. Here we conducted an analysis of 42 cohorts worldwide (N = 12,048), including 7,394 cognitively unimpaired (CU) participants, 2,177 participants with mild cognitive impairment (MCI) and 2,477 participants with dementia.

Image-Derived Blood Normalization of Antibody-Based TREM2 PET in Mouse Models of Amyloidosis and Myocardial Infarction.

The triggering receptor expressed on myeloid cells 2 (TREM2) plays a pivotal role in the activation of myeloid cells and is currently being investigated as a potential therapeutic target in several diseases. In this study, we established enhanced quantification of PET images of a Cu-labeled antibody-based PET radiotracer as a noninvasive tool for the assessment of TREM2 expression in the brain and peripheral organs of mice. We used TREM2 knockout mice that lack target expression to investigate data-driven blood normalization of PET images against percentage of injected dose normalization.

Microsurgical Lymphatic Vessel Transplantation for Chronic Lymphedema: Long-Term Evaluation of Volume Reduction and Lymphatic Transport Kinetics.

This study investigates long-term volume reduction after microsurgical autologous lymphatic vessel transplantation (LVT) in patients with chronic lymphoedema. Lymphoedema is caused by inadequate lymphatic drainage and leads to swelling, pain, and a reduced quality of life. Conservative treatments often show only limited success, which is why surgical procedures such as LVT are increasingly gaining in importance.

Association of integrated biomarkers and progression-free survival prediction in patients with gastroenteropancreatic neuroendocrine tumors undergoing [177Lu]Lu-DOTA-TATE therapy.

Integrated biomarkers that predict survival in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NET) receiving peptide receptor radionuclide therapy (PRRT) are still limited. This study aims to identify predictors of progression-free survival (PFS) in patients with GEP-NET undergoing two cycles of PRRT. This single-center retrospective study included 178 patients with GEP-NET (G1 and G2) who received at least two consecutive cycles of PRRT with [177Lu]Lu-DOTA-TATE and underwent somatostatin receptor (SSTR)-PET/CT before and after therapy.

Limitations of the radiotheranostic concept in neuroendocrine tumors due to lineage-dependent somatostatin receptor expression on hematopoietic stem and progenitor cells.

Radiopharmaceutical therapy (RPT) has become an effective treatment option for neuroendocrine tumors (NETs) and castration-resistant prostate cancer and is in clinical development for many indications. One of the major advantages of theranostic RPT is that the distribution of radiopharmaceuticals in the human body can be imaged, and radiation doses to the patient's organs can be calculated. However, accurate dosimetry may be fundamentally limited by microscopic heterogeneity of radiopharmaceutical distribution.

Brain Networks Route Neurodegeneration Patterns in Patients with Progressive Supranuclear Palsy.

Background: Progressive supranuclear palsy (PSP) is a neurodegenerative disease driven by 4-repeat τ pathology, which is thought to propagate across interconnected neurons.

Objectives: We hypothesized that interconnected brain regions exhibit correlated atrophy, and that atrophy propagates network-like from fast-declining epicenters to connected regions in PSP.

Methods: We combined resting-state functional magnetic resonance imaging (fMRI) connectomics with two independent 12-month longitudinal structural magnetic resonance imaging (MRI) datasets of PSP-Richardson syndrome (PSP-RS) patients (n/n = 114/90).

3D printing of radioactive wall-less PET phantoms improves threshold-based target delineation and quantification.

Background: Validation of threshold-based PET segmentation and PET quantification is typically performed with fillable phantoms. Theoretical considerations show that the inactive walls of the phantom cavities introduce a contrast dependence of the volume-reproducing threshold (VRT), potentially leading to segmentation errors and therefore miscalculations of target volumes. The goal of this study was to experimentally show the contrast independence of the VRT when using wall-less phantoms.

Cost-Effectiveness of [Lu]Lu-DOTATATE for the Treatment of Newly Diagnosed Advanced Gastroenteropancreatic Neuroendocrine Tumors: An Analysis Based on Results of the NETTER-2 Trial.

The recently published results of the NETTER-2 trial suggest the use of [Lu]Lu-DOTATATE as a new standard of care in first-line therapy of patients with grade 2 or 3, well-differentiated, advanced gastroenteropancreatic neuroendocrine tumors. The NETTER-2 trial found superior median progression-free survival (22.8 mo vs.

[F]SiTATE-PET/CT for detection of pheochromocytomas and paragangliomas: comparison of biochemical secretion, genotype and imaging metrics.

Background: Somatostatin-receptor (SSTR)-targeting PET/CT is widely used for diagnosis and disease monitoring of pheochromocytoma / paraganglioma (PPGL). The aim of this study was to assess the potential of the novel SSTR-targeting tracer [F]SiTATE in diagnosing PPGL by comparing imaging parameters to tumor marker levels and secretory activity in a small cohort of patients diagnosed with this rare tumor type.

Methods: This retrospective study included 34 patients with histologically confirmed PPGL who underwent [F]SiTATE-PET/CT at LMU University Hospital Munich between 10/2020 and 02/2024 as well as hormonal laboratory analysis within up to 100 days.

Insights into pathophysiology, biomarkers, and therapeutics in tauopathies: Proceedings of the Tau2024 Global Conference.

Recent years have seen major advances in tau-associated brain disorders through interdisciplinary research spanning molecular biology, neuroimaging, clinical trials, and therapeutic development. The Tau2024 Global Conference, hosted by the Alzheimer's Association, CurePSP, and Rainwater Charitable Foundation, showcased these efforts by bringing together researchers and experts worldwide to discuss the latest advancements in tau research. The conference aimed to attract talent and funding to study tauopathies, particularly among early-career researchers, and to foster interdisciplinary alignment and collaboration around challenges in tau research.

Associations between neuropsychological profile and regional brain FDG uptake in progressive supranuclear palsy.

BackgroundProgressive supranuclear palsy (PSP) is a rare neurodegenerative movement disorder clinically characterized by falls, axial rigidity, vertical supranuclear gaze palsy, bradykinesia, and cognitive decline. There is a relative lack of studies on the functional neuroimaging correlates of cognitive impairment in PSP.ObjectiveThis study investigated the relationship between regional cerebral glucose metabolism as assessed by static F-fluorodeoxyglucose positron emission tomography (FDG-PET) with global scaling and the profile of cognitive performance according to the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) test battery in a sample of PSP patients representative of clinical practice.

Plasma biomarkers of amyloid, tau & neuroinflammation in Alzheimer's disease and corticobasal syndrome.

Background: Blood-based biomarkers (BBBMs) could significantly facilitate the diagnosis of Alzheimer's disease (AD) and non-AD dementia by providing less invasive alternatives to cerebrospinal fluid (CSF) and positron emission tomography (PET) imaging.

Objective: This study investigated how well the BBBMs-amyloid-β (Aβ) 1-42/1-40 ratio, phosphorylated tau181 (pTau181), apolipoprotein E4 (ApoE4), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL)-reflect thorough clinical work-up validated by PET and CSF biomarkers in participants with AD (n = 27), Aβ-negative CBS (n = 26), and agematched healthy controls (HC) (n = 17).

Methods: Factor and correlation explored biomarker associations.

Partial volume effect correction impairs the diagnostic utility of [F]-THK-5351 PET in nonfluent-agrammatic variant primary progressive aphasia.

Objectives: Partial volume effects in positron emission tomography occur frequently in neurodegenerative diseases due to increasing cortical atrophy during the disease course, and fronto-temporal dementia is often characterized by severe atrophy. The aim of this study was to challenge partial volume effect correction (PVEC) in patients with nonfluent-agrammatic variant primary progressive aphasia (nfv-PPA) imaged with [F]-THK-5351 PET a marker of reactive neuroinflammatory astrogliosis as well as tau-binding.

Methods: Patients with nfv-PPA (n = 20) were imaged with [F]-THK-5351 PET accompanied by structural magnetic resonance tomography imaging (MRI).

Higher blood-brain barrier leakage in schizophrenia-spectrum disorders: A comparative dynamic contrast-enhanced magnetic resonance imaging study with healthy controls.

Background: Blood-brain barrier (BBB) disruptions are presumed to be implicated in schizophrenia-spectrum disorders (SSDs). Previous studies focused on cerebrospinal fluid (CSF) markers, which are imprecise for detecting subtle BBB disruption. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) enables sensitive investigation of subtle BBB leakage in vivo, yet remains unexplored in SSD research.

PET- and CT-Based Imaging Criteria for Response Assessment of Gastroenteropancreatic Neuroendocrine Tumors Under Radiopharmaceutical Therapy.

Despite well-documented limitations, current guidelines recommend the use of size-based RECIST 1.1 for response assessment of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) under radiopharmaceutical therapy (RPT). We hypothesize that functional criteria are superior to RECIST 1.

Exploring the origins of frequent tau-PET signal in vermal and adjacent regions.

Purpose: Off-target binding remains a significant challenge in tau-PET neuroimaging. While off-targets including monoamine oxidase enzymes and neuromelanin-containing cells have been identified, recent studies indicated a relevant binding of novel tau tracers to melanin-containing structures. To date, little is known about the effect of melanocytes in the meninges on tracer signals in brain PET data.

Perivascular space and white matter hyperintensities in Alzheimer's disease: associations with disease progression and cognitive function.

Background: Alzheimer's disease (AD) is the leading cause of dementia, characterized by the accumulation of amyloid-beta (Aβ) and neurofibrillary tangles. Recent studies emphasize the role of vascular factors, including the glymphatic system, in AD pathogenesis, particularly in Aβ clearance. The diffusion tensor image analysis along the perivascular space (DTI-ALPS; ALPS-Index) has emerged as a novel, non-invasive method to evaluate the glymphatic system in vivo, showing glymphatic insufficiency in AD.