Potential application of [F]AlF-PSMA-11 PET/CT in radioiodine refractory thyroid carcinoma.

Background: Patients diagnosed with radioiodine refractory (RAI-R) thyroid carcinoma (TC) have a significantly worse prognosis than patients with radiosensitive TC. These refractory malignancies are often dedifferentiated, hindering the effectiveness of iodine-based imaging. Additionally, the role of metabolic imaging using [F]FDG PET/CT is also limited in these cases, making adequate staging of RAI-R TC challenging.

Clinical impact of using [F]AlF-NOTA-octreotide PET/CT instead of [Ga]Ga-DOTA-SSA PET/CT: Secondary endpoint analysis of a multicenter, prospective trial.

[F]AlF-NOTA-octreotide ([F]AlF-OC) is a promising alternative for [Ga]Ga-DOTA-somatostatin analogs (SSAs) in positron emission tomography (PET) imaging of the somatostatin receptor (SSTR). Our aim is to assess changes in TNM staging and differences in patient management between [F]AlF-OC PET/CT and [Ga]Ga-DOTA-SSA PET/CT in the work-up of neuroendocrine tumor (NET) patients. Patients who underwent both [F]AlF-OC and [Ga]Ga-DOTA-TATE or [Ga]Ga-DOTA-NOC PET/CT in our multicenter study (Pauwels et al.

Anti-tau intrabodies: From anti-tau immunoglobulins to the development of functional scFv intrabodies.

Over the last decade, there has been a growing interest in intrabodies and their therapeutic potential. Intrabodies are antibody fragments that are expressed inside a cell to target intracellular antigens. In the context of intracellular protein misfolding and aggregation, such as tau pathology in Alzheimer's disease, intrabodies have become an interesting approach as there is the possibility to target early stages of aggregation.

Impact of F-PSMA-11 PET/CT on Management of Biochemical Recurrence and High-Risk Prostate Cancer Staging : F-PSMA-11 PET/CT and Impact on Prostate Cancer Management.

Purpose: In this study, we evaluated the impact of F-PSMA-11 PET/CT on the patient management plan in patients with primary or recurrent disease. Furthermore, a correlation between PET findings and other modalities was performed.

Procedures: In this prospective observational study, 60 prostate cancer patients (9 primary staging, 51 biochemical recurrence) were imaged with F-PSMA-11 PET/CT.

Hybrid imaging of complicating osteomyelitis in the peripheral skeleton.

Diagnosing complicating osteomyelitis (COM) is clinically challenging. Laboratory tests are of limited utility, and other than isolation of the offending organism, diagnostic imaging tests are of paramount importance. Nuclear Medicine techniques play an important role in noninvasive evaluation of osteomyelitis, using both single-photon emission tomography (SPECT) and positron emission tomography (PET) radiopharmaceuticals.

Passive immunotherapy with a novel antibody against 3pE-modified Aβ demonstrates potential for enhanced efficacy and favorable safety in combination with BACE inhibitor treatment in plaque-depositing mice.

The imbalance between production and clearance of amyloid β (Aβ) peptides and their resulting accumulation in the brain is an early and crucial step in the pathogenesis of Alzheimer's disease (AD). Therefore, Aβ is strongly positioned as a promising and extensively validated therapeutic target for AD. Investigational disease-modifying approaches aiming at reducing cerebral Aβ concentrations include prevention of de novo production of Aβ through inhibition of β-site amyloid precursor protein cleaving enzyme 1 (BACE1), and clearance of Aβ deposits via passive Aβ immunotherapy.

Spatiotemporal Evolution of Radiation Myositis on 18F-FDG PET/CT Following Hypofractionated Radiotherapy of Intramuscular Melanoma Metastases.

Radiation myositis is an infrequent late adverse effect of radiotherapy (RT), more commonly seen after hypofractionated regimens. We present the case of a 52-year-old woman with oligorecurrent metastatic melanoma who, several months after receiving local hypofractionated RT, developed a painful swelling at the irradiated site. As an integral part of routine oncologic follow-up, 18F-FDG PET/CT allowed accurate visualization of the affected region and when matched with RT treatment plans clearly illustrated their apparent overlap.

Shallow-depth sequencing of cell-free DNA for Hodgkin and diffuse large B-cell lymphoma (differential) diagnosis: a standardized approach with underappreciated potential.

Shallow-depth sequencing of cell-free DNA, a cheap and standardized approach to obtain molecular information on tumors non-invasively, is insufficiently explored for lymphoma diagnosis and disease follow-up. This study collected 318 samples, including longitudinal liquid and paired solid biopsies, from a prospectively recruited cohort of 38 Hodgkin lymphoma (HL) and 85 aggressive B-cell non- HL patients, represented by 81 diffuse large B-cell lymphoma (DLBCL) cases. Following sequencing, copy number alterations and viral read fractions were derived and analyzed.

Noise reduction using a Bayesian penalized-likelihood reconstruction algorithm on a time-of-flight PET-CT scanner.

Purpose: Q.Clear is a block sequential regularized expectation maximization (BSREM) penalized-likelihood reconstruction algorithm for PET. It tries to improve image quality by controlling noise amplification during image reconstruction.

Neural oscillations during cognitive processes in an App knock-in mouse model of Alzheimer's disease pathology.

Multiple animal models have been created to gain insight into Alzheimer's disease (AD) pathology. Among the most commonly used models are transgenic mice overexpressing human amyloid precursor protein (APP) with mutations linked to familial AD, resulting in the formation of amyloid β plaques, one of the pathological hallmarks observed in AD patients. However, recent evidence suggests that the overexpression of APP by itself can confound some of the reported observations.

Mass spectrometric characterization of intact desferal-conjugated monoclonal antibodies for immuno-PET imaging.

Rationale: Immuno-PET imaging may prove to be a diagnostic and progression/intervention biomarker for Alzheimer's disease (AD) with improved sensitivity and specificity. Immuno-PET imaging is based on the coupling of an antibody with a chelator that captures a radioisotope thus serving as an in-vivo PET ligand. A robust and quality controlled process for linking the chelator to the-antibody is fundamental for the success of this approach.

Diffusion kurtosis imaging allows the early detection and longitudinal follow-up of amyloid-β-induced pathology.

Background: Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the most common cause of dementia in the elderly population. In this study, we used the APP/PS1 transgenic mouse model to explore the feasibility of using diffusion kurtosis imaging (DKI) as a tool for the early detection of microstructural changes in the brain due to amyloid-β (Aβ) plaque deposition.

Methods: We longitudinally acquired DKI data of wild-type (WT) and APP/PS1 mice at 2, 4, 6 and 8 months of age, after which these mice were sacrificed for histological examination.

Evaluation of Small-Animal PET Outcome Measures to Detect Disease Modification Induced by BACE Inhibition in a Transgenic Mouse Model of Alzheimer Disease.

In this study, we investigated the effects of chronic administration of an inhibitor of the β-site amyloid precursor protein-cleaving enzyme 1 (BACE1) on Alzheimer-related pathology by multitracer PET imaging in transgenic APPPS1-21 (TG) mice. Wild-type (WT) and TG mice received vehicle or BACE inhibitor (60 mg/kg) starting at 7 wk of age. Outcome measures of brain metabolism, neuroinflammation, and amyloid-β pathology were obtained through small-animal PET imaging with F-FDG, F-peripheral benzodiazepine receptor (F-PBR), and F-florbetapir (F-AV45), respectively.

BACE1 Dynamics Upon Inhibition with a BACE Inhibitor and Correlation to Downstream Alzheimer's Disease Markers in Elderly Healthy Participants.

The β-site amyloid-β protein precursor (AβPP) cleaving enzyme-1 (BACE1) is the rate limiting enzyme in the generation of amyloid-β peptide (Aβ) from AβPP, one of the major pathways in Alzheimer's disease (AD) pathology. Increased BACE1 levels and activity have been reported in the brain of patients with sporadic AD. Therefore, changes of BACE1 levels in the cerebrospinal fluid (CSF) have also been investigated as a possible biomarker of the disease.

Parathyroid Adenoma Mimicking a Malignant Lymph Node on 18F-Choline PET-CT.

Prostate carcinoma is the most common cancer in men. After local therapy, disease recurs in many patients. A choline PET/CT is indicated in case of biochemical relapse of prostate carcinoma to determine the site of recurrence (local and/or distant) and to help select the next line of therapy.

Young to Middle-Aged Dogs with High Amyloid-β Levels in Cerebrospinal Fluid are Impaired on Learning in Standard Cognition tests.

Understanding differences in Alzheimer's disease biomarkers before the pathology becomes evident can contribute to an improved understanding of disease pathogenesis and treatment. A decrease in amyloid-β (Aβ)42 in cerebrospinal fluid (CSF) is suggested to be a biomarker for Aβ deposition in brain. However, the relevance of CSF Aβ levels prior to deposition is not entirely known.

Profiling the dynamics of CSF and plasma Aβ reduction after treatment with JNJ-54861911, a potent oral BACE inhibitor.

Objectives: Safety, tolerability, pharmacokinetics, and pharmacodynamics of a novel β-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitor, JNJ-54861911, were assessed after single and multiple dosing in healthy participants.

Methods: Two randomized, placebo-controlled, double-blind studies were performed using single and multiple ascending JNJ-54861911 doses (up to 14 days) in young and elderly healthy participants. Regular blood samples and frequent CSF samples, up to 36 hours after last dose, were collected to assess the pharmacokinetic and pharmacodynamic (Aβ, sAPPα,β,total levels) profiles of JNJ-54861911.

Impact of frequent cerebrospinal fluid sampling on Aβ levels: systematic approach to elucidate influencing factors.

Background: Cerebrospinal fluid (CSF) amyloid-beta (Aβ) peptides are predictive biomarkers for Alzheimer's disease and are proposed as pharmacodynamic markers for amyloid-lowering therapies. However, frequent sampling results in fluctuating CSF Aβ levels that have a tendency to increase compared with baseline. The impact of sampling frequency, volume, catheterization procedure, and ibuprofen pretreatment on CSF Aβ levels using continuous sampling over 36 h was assessed.

In Vivo Amyloid-β Imaging in the APPPS1-21 Transgenic Mouse Model with a (89)Zr-Labeled Monoclonal Antibody.

Introduction: The accumulation of amyloid-β is a pathological hallmark of Alzheimer's disease and is a target for molecular imaging probes to aid in diagnosis and disease monitoring. This study evaluated the feasibility of using a radiolabeled monoclonal anti-amyloid-β antibody (JRF/AβN/25) to non-invasively assess amyloid-β burden in aged transgenic mice (APPPS1-21) with μPET imaging.

Methods: We investigated the antibody JRF/AβN/25 that binds to full-length Aβ.

Synthesis and Evaluation of a Zr-89-Labeled Monoclonal Antibody for Immuno-PET Imaging of Amyloid-β Deposition in the Brain.

Purpose: The aim of this study was to evaluate the in vitro and in vivo characteristics of [(89)Zr]JRF/AβN/25, a radiolabeled monoclonal antibody directed against amyloid-β (Aβ).

Procedures: JRF/AβN/25 was labeled with (89)Zr following modification with desferal. The affinity of the tracer for Aβ1-40 was determined in a saturation binding assay.

Monitoring activities of daily living using Wireless Acoustic Sensor Networks in clean and noisy conditions.

This work examines the use of a Wireless Acoustic Sensor Network (WASN) for the classification of clinically relevant activities of daily living (ADL) of elderly people. The aim of this research is to automatically compile a summary report about the performed ADLs which can be easily interpreted by caregivers. In this work, the classification performance of the WASN will be evaluated in both clean and noisy conditions.

Diagnostic Accuracy of Cerebrospinal Fluid Amyloid-β Isoforms for Early and Differential Dementia Diagnosis.

Background: Overlapping cerebrospinal fluid biomarkers (CSF) levels between Alzheimer's disease (AD) and non-AD patients decrease differential diagnostic accuracy of the AD core CSF biomarkers. Amyloid-β (Aβ) isoforms might improve the AD versus non-AD differential diagnosis.

Objective: To determine the added diagnostic value of Aβ isoforms, Aβ(1-37), Aβ(1-38), and Aβ(1-40), as compared to the AD CSF biomarkers Aβ(1-42), T-tau, and P-tau(181P).

Comparison of two different methods for measurement of amyloid-β peptides in cerebrospinal fluid after BACE1 inhibition in a dog model.

Beta-secretase is the first cleavage enzyme of amyloid-β protein precursor (AβPP) in the amyloidogenic pathway, leading to the formation of the plaque forming Amyloid-β (Aβ)1-42 peptide. BACE (beta-site AβPP cleaving enzyme) 1 inhibition is therefore considered to be a promising disease modifying therapy for Alzheimer's disease. An early assessment of the in vivo activity of BACE inhibitors was done in dogs since AβPP processing is the same as in humans and this species easily enables longitudinal cerebrospinal fluid (CSF) sampling.