Longitudinal accumulation of glial activation measured by TSPO-PET predicts later brain atrophy in multiple sclerosis.

In multiple sclerosis (MS), accumulation of disability is driven by CNS-compartmentalized inflammation. This inflammatory process involves activated microglia and astrocytes, which contribute to neuroaxonal damage which in turn accelerates disease progression. Activated glial cells express 18-kDa translocator protein (TSPO), and TSPO-binding radioligands and positron emission tomography (PET) imaging can be used to quantitate glial activation in vivo.

Rapid cleavage of 6-[F]fluoronicotinic acid prosthetic group governs BT12 glioblastoma xenograft uptake: implications for radiolabeling design of biomolecules.

Background: Peptides radiolabeled with fluorine-18 are frequently synthesized using prosthetic groups. Among them, activated esters of 6-[F]fluoronicotinic acid ([F]FNA) have been prepared and successfully employed for F-labeling of diverse biomolecules, including peptides. The utility of [F]FNA as a prosthetic compound has been demonstrated in both preclinical and clinical settings, including radiopharmaceuticals targeting prostate-specific membrane antigen and poly(ADP ribose) polymerase inhibitors.

Utilizing Monocarboxylate Transporter 1-Mediated Blood-Brain Barrier Penetration for Glioblastoma Positron Emission Tomography Imaging with 6-[F]Fluoronicotinic Acid.

Glioblastoma is the most malignant brain tumor in adults, and its prognosis remains dismal. The blood-brain barrier impedes the effectiveness of many drugs, which are otherwise effective for cancer treatment. Monocarboxylate transporter 1 (MCT1) is expressed on endothelial and glioblastoma cells.

Circulating N-Acetylaspartate Levels Associate with Measures of Peripheral and Tissue-Specific Insulin Sensitivity.

N-acetylaspartate (NAA) is the second most abundant metabolite in the human brain. Quantifiable amounts of NAA are also present in the blood, but its role in the peripheral tissues is largely unknown. First, we determined the acute effects of insulin administration on NAA concentrations; second, we assessed whether circulating NAA levels associate with markers of central and peripheral insulin sensitivity.

Macrophage mannose receptor CD206-targeted PET imaging in experimental acute myocardial infarction.

Background: The macrophage mannose receptor (CD206) is expressed predominantly on the surface of M2-type macrophages, which play a role in resolution of inflammation after myocardial injury. The purpose of this study was to evaluate the utility of CD206-targeted PET tracer Al[F]F-NOTA-D10CM, a fluorinated mannosylated dextran derivative, for imaging immune responses after experimental acute myocardial infarction (MI).

Results: Flow cytometry revealed selective binding of Alexa-488-NOTA-D10CM to human M2-polarized macrophages derived from blood monocytes compared to M1 macrophages.

Striatal cue-reactivity and neurotransmitter function in gambling disorder.

Background: Abnormal striatal cue reactivity is one of the neurobiological hallmarks of substance use disorders (SUDs). Cue reactivity is associated with relapse, prompting efforts to target its underlying mechanisms with therapeutic interventions. However, the neural correlates of cue reactivity in behavioral addictions, such as gambling disorder (GD), remain poorly understood.

Comparison of Automatic Segmentation and Preprocessing Approaches for Dynamic Total-Body 3D Pet Images with Different Pet Tracers.

Segmentation is a routine step in PET image analysis, and few automatic tools have been developed for it. However, excluding supervised methods with their own limitations, they are typically designed for older, small images and the implementations are no longer publicly available. Here, we test if different commonly used building blocks of the automatic methods work with large modern total-body PET images.

Biological Evaluation of Molecular Spherical Nucleic Acids: Targeting Tumors via a Hybridization-Based Folate Decoration.

Folate receptors (FRs), membrane-bound proteins that bind specifically to folate with high affinity, are overexpressed by various cancer types and are therefore used as targets for delivery of therapeutic agents. Molecular spherical nucleic acids (MSNAs) are dendritic formulations of oligonucleotides (ONs) that may have advantages over linear parent ONs with respect to delivery properties. Here, we assembled folate-decorated MSNAs, site-specifically radiolabeled them, and then biologically evaluated their effects in mice bearing HCC1954 breast cancer xenograft tumors.

Exercise training partly ameliorates cardiac dysfunction in mice during doxorubicin treatment of breast cancer.

Introduction: Doxorubicin is a chemotherapeutic drug used to treat various cancers. Exercise training (ET) can attenuate some cardiotoxic effects of doxorubicin (DOX) in tumor-free animals. However, the ET effects on cardiac function and glucose metabolism in DOX-treated breast cancer models remain unclear.

Anorexia nervosa is associated with higher brain mu-opioid receptor availability.

Anorexia nervosa (AN) is a severe psychiatric disorder, characterized by restricted eating, fear to gain weight, and a distorted body image. Mu-opioid receptor (MOR) functions as a part of complex opioid system and supports both homeostatic and hedonic control of eating behavior. Thirteen patients with AN and thirteen healthy controls (HC) were included in this study.

P2X -receptor binding in new-onset and secondary progressive MS - a [C]SMW139 PET study.

Background: PET imaging of activated microglia has improved our understanding of the pathology behind disability progression in MS, and pro-inflammatory microglia at 'smoldering' lesion rims have been implicated as drivers of disability progression. The P2X R is upregulated in the cellular membranes of activated microglia. A single-tissue dual-input model was applied to quantify P2X R binding in the normal appearing white matter, perilesional areas and thalamus among progressive MS patients, healthy controls and newly diagnosed relapsing MS patients.

Regular Exercise Training Induces More Changes on Intestinal Glucose Uptake from Blood and Microbiota Composition in Leaner Compared to Heavier Individuals in Monozygotic Twins Discordant for BMI.

Background/objectives: Obesity impairs intestinal glucose uptake (GU) (intestinal uptake of circulating glucose from blood) and alters gut microbiome. Exercise improves intestinal insulin-stimulated GU and alters microbiome. Genetics influence the risk of obesity and gut microbiome.

Effects of Obesity and Exercise on Hepatic and Pancreatic Lipid Content and Glucose Metabolism: PET Studies in Twins Discordant for BMI.

Obesity and sedentarism are associated with increased liver and pancreatic fat content (LFC and PFC, respectively) as well as impaired organ metabolism. Exercise training is known to decrease organ ectopic fat but its effects on organ metabolism are unclear. Genetic background affects susceptibility to obesity and the response to training.

Switching the Chemoselectivity in the Preparation of [F]FNA--CooP, a Free Thiol-Containing Peptide for Targeted Positron Emission Tomography Imaging of Fatty Acid Binding Protein 3.

Fatty acid binding protein 3 (FABP3) is expressed both in tumor cells and in the tumor vasculature, making it a potential target for medical imaging and therapy. In this study, we aimed to radiolabel a CooP peptide with a free amino and thiol group, and evaluate the radiolabeled product [F]FNA--CooP for imaging FABP3 expression in breast cancer brain metastases by positron emission tomography. [F]FNA--CooP was prepared by highly chemoselective -acylation and characterized using different chemical approaches.

Evaluation of bone marrow glucose uptake and adiposity in male rats after diet and exercise interventions.

Objectives: Obesity impairs bone marrow (BM) glucose metabolism. Adult BM constitutes mostly of adipocytes that respond to changes in energy metabolism by modulating their morphology and number. Here we evaluated whether diet or exercise intervention could improve the high-fat diet (HFD) associated impairment in BM glucose uptake (BMGU) and whether this associates with the morphology of BM adipocytes (BMAds) in rats.

Non-invasive quantification of stem cell-derived islet graft size and composition.

Aims/hypothesis: Stem cell-derived islets (SC-islets) are being used as cell replacement therapy for insulin-dependent diabetes. Non-invasive long-term monitoring methods for SC-islet grafts, which are needed to detect misguided differentiation in vivo and to optimise their therapeutic effectiveness, are lacking. Positron emission tomography (PET) has been used to monitor transplanted primary islets.

New improved radiometabolite analysis method for [F]FTHA from human plasma: a test-retest study with postprandial and fasting state.

Background: Fatty acid uptake can be measured using PET and 14-(R,S)-[F]fluoro-6-thia-heptadecanoic acid ([F]FTHA). However, the relatively rapid rate of [F]FTHA metabolism significantly affects kinetic modeling of tissue uptake. Thus, there is a need for accurate chromatographic methods to analyze the unmetabolized [F]FTHA (parent fraction).

Macrophage mannose receptor CD206 targeting of fluoride-18 labeled mannosylated dextran: A validation study in mice.

Purpose: Aluminum fluoride-18-labeled 1,4,7-triazacyclononane-1,4,7-triacetic acid-conjugated mannosylated dextran derivative (Al[F]F-NOTA-D10CM) is a new tracer for PET imaging. We report here on in vitro and in vivo validation of the tracer's ability to target the macrophage mannose receptor CD206.

Methods: First, the uptake of intravenously (i.

In-target production of [C]CH from a nitrogen/hydrogen gas target as a function of beam current, irradiation time, and target temperature.

Background: Production of [C]CH from gas targets is notorious for weak performance with respect to yield, especially when using high beam currents. Post-target conversion of [C]CO to [C]CH is a widely used roundabout method in C-radiochemistry, but the added complexity increase the challenge to control carrier carbon. Thus in-target-produced [C]CH is superior with respect to molar activity.

Radiosynthesis, structural identification and in vitro tissue binding study of [F]FNA-S-ACooP, a novel radiopeptide for targeted PET imaging of fatty acid binding protein 3.

Background: Fatty acid binding protein 3 (FABP3) is a target with clinical relevance and the peptide ligand ACooP has been identified for FABP3 targeting. ACooP is a linear decapeptide containing a free amino and thiol group, which provides opportunities for conjugation. This work is to develop methods for radiolabeling of ACooP with fluorine-18 (F) for positron emission tomography (PET) applications, and evaluate the binding of the radiolabeled ACooP in human tumor tissue sections with high FABP3 expression.

Evaluation of PET imaging as a tool for detecting neonatal hypoxic-ischemic encephalopathy in a preclinical animal model.

Unlabelled: Hypoxic-ischemic encephalopathy due to insufficient oxygen delivery to brain tissue is a leading cause of death or severe morbidity in neonates. The early recognition of the most severely affected individuals remains a clinical challenge. We hypothesized that hypoxic-ischemic injury can be detected using PET radiotracers for hypoxia ([F]EF5), glucose metabolism ([F]FDG), and inflammation ([F]F-DPA).

Segmentation of Dynamic Total-Body [F]-FDG PET Images Using Unsupervised Clustering.

Clustering time activity curves of PET images have been used to separate clinically relevant areas of the brain or tumours. However, PET image segmentation in multiorgan level is much less studied due to the available total-body data being limited to animal studies. Now, the new PET scanners providing the opportunity to acquire total-body PET scans also from humans are becoming more common, which opens plenty of new clinically interesting opportunities.

Tetrazine Glycoconjugate for Pretargeted Positron Emission Tomography Imaging of -Cyclooctene-Functionalized Molecular Spherical Nucleic Acids.

Pretargeted concept in positron emission tomography (PET) together with bioorthogonal chemistry is an elegant solution to study processes with slow pharmacokinetics by utilizing radiotracers labeled with short-lived radionuclides. Namely, radiotracers based on tetrazine ligation with -cyclooctene (TCO) via the inverse electron demand Diels-Alder (IEDDA) reaction have become a state-of-the-art for the pretargeted PET imaging. For radiolabeling of tetrazine scaffolds, indirect radiofluorination methods are often preferred, as tetrazines are vulnerable to harsh conditions typically necessary for the direct radiofluorination.