Exenatide and glucagon co-infusion increases myocardial glucose uptake and improves markers of diastolic dysfunction in adults with type 2 diabetes.

Type 2 diabetes (T2D) significantly increases the risk of heart failure, a major cause of hospitalisation and increased morbidity and mortality. Dual and multi-agonist synthetic peptides at the GLP-1 and glucagon receptor are in clinical development as potential new treatments for a range of chronic metabolic conditions including T2D. Here, we aimed to explore the effects of GLP-1 and glucagon dual receptor agonism on myocardial glucose uptake (MGU) and myocardial function in T2D.

Alterations in cerebral perfusion and substrate metabolism in type 2 diabetes: interactions with APOE-ε4.

Aims/hypothesis: Epidemiological studies indicate that type 2 diabetes increases the risk for Alzheimer's disease. Alterations in cerebral metabolism have been proposed as a potential mechanism underlying this association. A better understanding of these metabolic changes may elucidate potential pathways linking type 2 diabetes to Alzheimer's disease.

SGLT2 Inhibitor Dapagliflozin Increases Skeletal Muscle and Brain Fatty Acid Uptake in Individuals With Type 2 Diabetes: A Randomized Double-Blind Placebo-Controlled Positron Emission Tomography Study.

Objective: The aim of this study was to investigate the impact of the sodium-glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin on tissue fatty acid (FA) uptake in the skeletal muscle, brain, small intestine, and subcutaneous and visceral adipose tissue of individuals with type 2 diabetes by using positron emission tomography (PET).

Research Design And Methods: In a 6-week randomized double-blind placebo-controlled trial, 53 patients with type 2 diabetes treated with metformin received either 10 mg dapagliflozin or placebo daily. Tissue FA uptake was quantified at baseline and end of treatment with PET and the long-chain FA analog radiotracer 14(R,S)-[18F]fluoro-6-thia-heptadecanoic acid.

Effects of 6 weeks of treatment with dapagliflozin, a sodium-glucose co-transporter-2 inhibitor, on myocardial function and metabolism in patients with type 2 diabetes: A randomized, placebo-controlled, exploratory study.

Aim: To explore the early effects of dapagliflozin on myocardial function and metabolism in patients with type 2 diabetes without heart failure.

Materials And Methods: Patients with type 2 diabetes on metformin treatment were randomized to double-blind, 6-week placebo or dapagliflozin 10 mg daily treatment. Investigations included cardiac function and structure with myocardial resonance imaging; cardiac oxygen consumption, perfusion and efficiency with [ C]-acetate positron emission tomography (PET); and cardiac and hepatic fatty acid uptake with [ F]-6-thia-heptadecanoic acid PET, analysed by ANCOVA as least square means with 95% confidence intervals.

Pre- and postoperative Ga-DOTATOC positron emission tomography for hormone-secreting pituitary neuroendocrine tumours.

Objectives: Somatostatin receptors (SSTRs) are potential targets for detecting pituitary neuroendocrine tumours (PitNETs) that can be visualized effectively with Ga-labelled PET tracers. With this study, we have evaluated the diagnostic properties of such a tracer, Ga-DOTATOC, in patients with hormone-producing PitNETs before and after surgery.

Design/methods: This prospective case-control study presents preoperative positron emission tomography (PET) and histopathological data in 18 patients with somatotroph (n = 8), corticotroph (n = 7) and thyrotroph (n = 3) PitNETs.

Pharmacokinetic modelling for the simultaneous assessment of perfusion and F-flutemetamol uptake in cerebral amyloid angiopathy using a reduced PET-MR acquisition time: Proof of concept.

Purpose: Cerebral amyloid angiopathy (CAA) is a cerebral small vessel disease associated with perivascular β-amyloid deposition. CAA is also associated with strokes due to lobar intracerebral haemorrhage (ICH). F-flutemetamol amyloid ligand PET may improve the early detection of CAA.

Validation of a spatial normalization method using a principal component derived adaptive template for [F]florbetaben PET.

Quantification may help in the context of amyloid-β positron emission tomography (PET). Quantification typically requires that PET images be spatially normalized, a process that can be subject to bias. We herein aimed to test whether a principal component approach (PCA) previously applied to [F]flutemetamol PET extends to [F]florbetaben.

Correction to: Different aspects of Alzheimer's disease-related amyloid β-peptide pathology and their relationship to amyloid positron emission tomography imaging and dementia.

An amendment to this paper has been published and can be accessed via the original article.

Disturbances in brain energy metabolism in insulin resistance and diabetes and Alzheimer's disease - Learnings from brain imaging biomarkers.

Medical imaging techniques, such as structural and functional magnetic resonance imaging and positron emission tomography, have been used to gain a better understanding of the alterations of the metabolic processes in the brain relating to type 2 diabetes melltius, insulin resistance and Alzheimer's disease. These studies have shown that there are several similarities in the effects that these seemingly disparate diseases have on the brain, and that some of the abnormalities are reversed by metabolic interventions. This review provides an overview of the overlap between these diseases using medical imaging, focusing on glucose metabolism, mitochondrial function and lipid metabolism.

Simulating the effect of cerebral blood flow changes on regional quantification of [F]flutemetamol and [F]florbetaben studies.

Global and regional changes in cerebral blood flow (CBF) can result in biased quantitative estimates of amyloid load by PET imaging. Therefore, the current simulation study assessed effects of these changes on amyloid quantification using a reference tissue approach for [F]flutemetamol and [F]florbetaben. Previously validated pharmacokinetic rate constants were used to simulate time-activity curves (TACs) corresponding to full dynamic and dual-time-window acquisition protocols.

Lower Ga-DOTATOC uptake in nonfunctioning pituitary neuroendocrine tumours compared to normal pituitary gland-A proof-of-concept study.

Objectives: Ga-DOTATOC PET targets somatostatin receptors (SSTRs) and is well established for the detection of SSTR-expressing tumors, such as gastrointestinal neuroendocrine tumors. Pituitary adenomas, recently designated as pituitary neuroendocrine tumors (PitNETs), also express SSTRs, but there has been no previous evaluations of Ga-DOTATOC PET in PitNET patients. The aim of this pilot study was to evaluate the diagnostic properties of Ga-DOTATOC PET in the most common PitNET, ie non-functioning (NF)-PitNET.

Different aspects of Alzheimer's disease-related amyloid β-peptide pathology and their relationship to amyloid positron emission tomography imaging and dementia.

Alzheimer's disease (AD)-related amyloid β-peptide (Aβ) pathology in the form of amyloid plaques and cerebral amyloid angiopathy (CAA) spreads in its topographical distribution, increases in quantity, and undergoes qualitative changes in its composition of modified Aβ species throughout the pathogenesis of AD. It is not clear which of these aspects of Aβ pathology contribute to AD progression and to what extent amyloid positron emission tomography (PET) reflects each of these aspects. To address these questions three cohorts of human autopsy cases (in total n = 271) were neuropathologically and biochemically examined for the topographical distribution of Aβ pathology (plaques and CAA), its quantity and its composition.

Overeating Saturated Fat Promotes Fatty Liver and Ceramides Compared With Polyunsaturated Fat: A Randomized Trial.

Context: Saturated fatty acid (SFA) vs polyunsaturated fatty acid (PUFA) may promote nonalcoholic fatty liver disease by yet unclear mechanisms.

Objective: To investigate if overeating SFA- and PUFA-enriched diets lead to differential liver fat accumulation in overweight and obese humans.

Design: Double-blind randomized trial (LIPOGAIN-2).

Optimized dual-time-window protocols for quantitative [F]flutemetamol and [F]florbetaben PET studies.

Background: A long dynamic scanning protocol may be required to accurately measure longitudinal changes in amyloid load. However, such a protocol results in a lower patient comfort and scanning efficiency compared to static scans. A compromise can be achieved by implementing dual-time-window protocols.

Synaptic vesicle protein 2A as a potential biomarker in synaptopathies.

Measuring synaptic density in vivo using positron emission tomography (PET) imaging-based biomarkers targeting the synaptic vesicle protein 2A (SV2A) has received much attention recently due to its potential research and clinical applications in synaptopathies, including neurodegenerative and psychiatric diseases. Fluid-based biomarkers in proteinopathies have previously been suggested to provide information on pathology and disease status that is complementary to PET-based measures, and the same can be hypothesized with respect to SV2A. This review provides an overview of the current state of SV2A PET imaging as a biomarker of synaptic density, the potential role of fluid-based biomarkers for SV2A, and related future perspectives.

Detection of Alzheimer's Disease.

Recent revisions to the diagnostic criteria for Alzheimer's disease (AD) incorporated conceptual advances in the field. Specifically, AD is now recognized to encompass a continuum, spanning from preclinical (accruing brain pathology in the absence of symptoms) through symptomatic predementia (prodromal AD, mild cognitive impairment) and dementia phases. The role of biological markers (biomarkers) of both the underlying molecular pathologies and related neurodegenerative changes has also been acknowledged.

Estimation of amyloid distribution by [F]flutemetamol PET predicts the neuropathological phase of amyloid β-protein deposition.

The deposition of the amyloid β-protein (Aβ) in senile plaques is one of the histopathological hallmarks of Alzheimer's disease (AD). Aβ-plaques arise first in neocortical areas and, then, expand into further brain regions in a process described by 5 phases. Since it is possible to identify amyloid pathology with radioactive-labeled tracers by positron emission tomography (PET) the question arises whether it is possible to distinguish the neuropathological Aβ-phases with amyloid PET imaging.

Regional times to equilibria and their impact on semi-quantification of [F]AV-1451 uptake.

The semi-quantitative estimate standardised uptake value ratios (SUVR) correlate well with specific binding of the tracer expressed as distribution volume ratios (DVR) for the tau positron emission tomography tracer [F]AV-1451 uptake and are therefore widely used as proxy for tracer binding. With regard to tracer kinetic modelling, there exists a time point when SUVR deviates minimally from DVR, occurring when the specific binding reaches a transient equilibrium Here, we have investigated whether the time to equilibrium affects the agreement between SUVR and DVR across different brain regions. We show that the time required to reach equilibrium differs across brain regions, resulting in region-specific biases.

Altered Glucose Uptake in Muscle, Visceral Adipose Tissue, and Brain Predict Whole-Body Insulin Resistance and may Contribute to the Development of Type 2 Diabetes: A Combined PET/MR Study.

We assessed glucose uptake in different tissues in type 2 diabetes (T2D), prediabetes, and control subjects to elucidate its impact in the development of whole-body insulin resistance and T2D. Thirteen T2D, 12 prediabetes, and 10 control subjects, matched for age and BMI, underwent OGTT and abdominal subcutaneous adipose tissue (SAT) biopsies. Integrated whole-body F-FDG PET and MRI were performed during a hyperinsulinemic euglycemic clamp to asses glucose uptake rate (MRglu) in several tissues.

Update on biomarkers for amyloid pathology in Alzheimer's disease.

At the center of Alzheimer's disease pathogenesis is the aberrant aggregation of amyloid-β (Aβ) into oligomers, fibrils and plaques. Effective monitoring of Aβ deposition directly in patients is essential to assist anti-Aβ therapeutics in target engagement and participant selection. In the advent of approved anti-Aβ therapeutics, biomarkers will become of fundamental importance in initiating treatments having disease modifying effects at the earliest stage.

Whole-Body Imaging of Tissue-specific Insulin Sensitivity and Body Composition by Using an Integrated PET/MR System: A Feasibility Study.

Purpose To develop, evaluate, and demonstrate the feasibility of a whole-body protocol for simultaneous assessment of tissue-specific insulin-mediated fluorine 18 (F) fluorodeoxyglucose (FDG) influx rates, tissue depots, and whole-body insulin sensitivity (referred to as the M value). Materials and Methods An integrated positron emission tomography (PET)/magnetic resonance (MR) imaging system combined with hyperinsulinemic euglycemic clamp (HEC) was used. Dynamic whole-body PET imaging was used to determine the insulin-mediated F-FDG tissue influx rate (K) in the whole-body region by using the Patlak method.

Quantitative positron emission tomography in brain research.

The application of positron emission tomography (PET) in brain research has increased substantially during the past 20years, and is still growing. PET provides a unique insight into physiological and pathological processes in vivo. In this article we introduce the fundamentals of PET, and the methods available for acquiring quantitative estimates of the parameters of interest.

Brain uptake and safety of Flutemetamol F 18 injection in Japanese subjects with probable Alzheimer's disease, subjects with amnestic mild cognitive impairment and healthy volunteers.

Objective: This Phase 2 study assessed the performance of positron emission tomography (PET) brain images made with Flutemetamol F 18 Injection in detecting β-amyloid neuritic plaques in Japanese subjects.

Methods: Seventy subjects (25 with probable Alzheimer's disease (pAD), 20 with amnestic mild cognitive impairment (aMCI), and 25 cognitively normal healthy volunteers[HVs]) underwent PET brain imaging after intravenous Flutemetamol F 18 Injection (185 MBq). Images were interpreted as normal or abnormal for neuritic plaque density by each of five non-Japanese and five Japanese readers who were blinded to clinical data.

Post-mortem histopathology underlying β-amyloid PET imaging following flutemetamol F 18 injection.

In vivo imaging of fibrillar β-amyloid deposits may assist clinical diagnosis of Alzheimer's disease (AD), aid treatment selection for patients, assist clinical trials of therapeutic drugs through subject selection, and be used as an outcome measure. A recent phase III trial of [F]flutemetamol positron emission tomography (PET) imaging in 106 end-of-life subjects demonstrated the ability to identify fibrillar β-amyloid by comparing in vivo PET to post-mortem histopathology. Post-mortem analyses demonstrated a broad and continuous spectrum of β-amyloid pathology in AD and other dementing and non-dementing disease groups.