Vascular adhesion protein-1-targeted PET imaging in autoimmune myocarditis.

Background: Vascular adhesion protein-1 (VAP-1) is an adhesion molecule and primary amine oxidase, and Gallium-68-labeled 1,4,7,10-tetraazacyclododecane-N,N',N″,N‴-tetra-acetic acid conjugated sialic acid-binding immunoglobulin-like lectin 9 motif containing peptide ([Ga]Ga-DOTA-Siglec-9) is a positron emission tomography (PET) tracer targeting VAP-1. We evaluated the feasibility of PET imaging with [Ga]Ga-DOTA-Siglec-9 for the detection of myocardial lesions in rats with autoimmune myocarditis.

Methods: Rats (n = 9) were immunized twice with porcine cardiac myosin in complete Freund's adjuvant.

Dissecting the polygenic basis of atherosclerosis via disease-associated cell state signatures.

Coronary artery disease (CAD) is a pandemic disease where up to half of the risk is explained by genetic factors. Advanced insights into the genetic basis of CAD require deeper understanding of the contributions of different cell types, molecular pathways, and genes to disease heritability. Here, we investigate the biological diversity of atherosclerosis-associated cell states and interrogate their contribution to the genetic risk of CAD by using single-cell and bulk RNA sequencing (RNA-seq) of mouse and human lesions.

Preclinical Evaluation of Zr-Desferrioxamine-Bexmarilimab, a Humanized Antibody Against Common Lymphatic Endothelial and Vascular Endothelial Receptor-1, in a Rabbit Model of Renal Fibrosis.

Bexmarilimab is a new humanized monoclonal antibody against common lymphatic endothelial and vascular endothelial receptor-1 (CLEVER-1) and is in clinical trials for macrophage-guided cancer immunotherapy. In addition being associated with cancer, CLEVER-1 is also associated with fibrosis. To facilitate prospective human PET studies, we preclinically evaluated Zr-labeled bexmarilimab in rabbits.

[C]carfentanil PET imaging for studying the peripheral opioid system in vivo: effect of photoperiod on mu-opioid receptor availability in brown adipose tissue.

Purpose: Photoperiod determines the metabolic activity of brown adipose tissue (BAT) and affects the food intake and body mass of mammals. Sympathetic innervation of the BAT controls thermogenesis and facilitates physiological adaption to seasonal changes, but the exact mechanism remains elusive. Previous studies have shown that central opioid signaling regulates BAT thermogenesis, and that the expression of the brain mu-opioid receptor (MOR) varies seasonally.

Corrigendum: Exploiting Glutamine Consumption in Atherosclerotic Lesions by Positron Emission Tomography Tracer (2,4)-4-F-Fluoroglutamine.

[This corrects the article DOI: 10.3389/fimmu.2022.

Exploiting Glutamine Consumption in Atherosclerotic Lesions by Positron Emission Tomography Tracer (2,4)-4-F-Fluoroglutamine.

Increased glutamine metabolism by macrophages is associated with development of atherosclerotic lesions. Positron emission tomography/computed tomography (PET/CT) with a glutamine analog (2S,4)-4-F-fluoroglutamine (F-FGln) allows quantification of glutamine consumption . Here, we investigated uptake of F-FGln by atherosclerotic lesions in mice and compared the results with those obtained using the glucose analog 2-deoxy-2-F-fluoro--glucose (F-FDG).

Evaluation of [Ga]Ga-NODAGA-RGD for PET Imaging of Rat Autoimmune Myocarditis.

The Gallium-labeled 1,4,7-triazacyclononane-1-glutaric acid-4,7-diacetic acid conjugated radiolabelled arginine-glycine-aspartic acid peptide ([Ga]Ga-NODAGA-RGD) is a positron emission tomography (PET) tracer binding to cell surface receptor αβ integrin that is upregulated during angiogenesis and inflammation. We studied whether αβ targeting PET imaging can detect myocardial inflammation in a rat model of autoimmune myocarditis. To induce myocarditis, rats ( = 8) were immunized with porcine cardiac myosin in complete Freund's adjuvant on days 0 and 7.

Comparison of: (2,4)-4-[F]Fluoroglutamine, [C]Methionine, and 2-Deoxy-2-[F]Fluoro--Glucose and Two Small-Animal PET/CT Systems Imaging Rat Gliomas.

Purpose: The three positron emission tomography (PET) imaging compounds: (2,4)-4-[F]Fluoroglutamine ([F]FGln), -[methyl-C]Methionine ([C]Met), and 2-deoxy-2-[F]fluoro--glucose ([F]FDG) were investigated to contrast their ability to image orthotopic BT4C gliomas in BDIX rats. Two separate small animal imaging systems were compared for their tumor detection potential. Dynamic acquisition of [F]FGln was evaluated with multiple pharmacokinetic models for future quantitative comparison.

Evaluation of glucagon-like peptide-1 receptor expression in nondiabetic and diabetic atherosclerotic mice using PET tracer Ga-NODAGA-exendin-4.

Cardiovascular effects of glucagon-like peptide-1 receptor (GLP-1R) agonist therapies are potentially mediated by anti-inflammatory effects on atherosclerosis. Our study demonstrates that Ga-NODAGA-exendin-4, a radioligand specifically targeting GLP-1R, detects GLP-1R expression in inflamed atherosclerotic lesions in nondiabetic and diabetic hypercholesterolemic mice. Immunofluorescence staining suggests that GLP-1R is primarily localized in M2 macrophages in lesions.

Efficacy and tolerability of folate-aminopterin therapy in a rat focal model of multiple sclerosis.

Background: Activated macrophages in the experimental model of multiple sclerosis (MS) express folate receptor-β (FR-β), representing a promising target for the treatment of MS. Here, we both evaluated the efficacy of a novel folate-aminopterin construct (EC2319) in a rat focal model of multiple sclerosis (MS) and investigated the utility of Ga-labeled 1,4,7-triazacyclononane-1,4,7-triacetic acid-conjugated folate (Ga-FOL) for assessing inflammatory lesions. In addition, we investigated whether FR-β is expressed in the brain of patients with MS.

Seasonal Variation in the Brain μ-Opioid Receptor Availability.

Seasonal rhythms influence mood and sociability. The brain μ-opioid receptor (MOR) system modulates a multitude of seasonally varying socioemotional functions, but its seasonal variation remains elusive with no previously reported evidence. Here, we first conducted a cross-sectional study with previously acquired human [C]carfentanil PET imaging data (132 male and 72 female healthy subjects) to test whether there is seasonal variation in MOR availability.

Radiosynthesis and preclinical evaluation of [Ga]Ga-NOTA-folate for PET imaging of folate receptor β-positive macrophages.

Folate receptor β (FR-β), a marker expressed on macrophages, is a promising target for imaging of inflammation. Here, we report the radiosynthesis and preclinical evaluation of [Ga]Ga-NOTA-folate (Ga-FOL). After determining the affinity of Ga-FOL using cells expressing FR-β, we studied atherosclerotic mice with Ga-FOL and F-FDG PET/CT.

Effects of dipeptidyl peptidase 4 inhibition on inflammation in atherosclerosis: A F-fluorodeoxyglucose study of a mouse model of atherosclerosis and type 2 diabetes.

Background And Aims: Dipeptidyl peptidase 4 (DPP-4) inhibitors have anti-inflammatory and atheroprotective effects. We evaluated the effects of the DPP-4 inhibitor linagliptin on atherosclerotic plaque and hepatic inflammation using histology and 2-deoxy-2-[F]-fluoro-d-glucose (F-FDG), a positron emission tomography tracer of inflammation, in a mouse model of hypercholesterolemia and type 2 diabetes.

Methods: Igf2/LdlrApob mice were fed a high-fat diet (HFD) for 8 weeks and then randomly allocated to receive HFD (n = 14), or HFD with added linagliptin (n = 15) for additional 12 weeks.

Folate Receptor β-Targeted PET Imaging of Macrophages in Autoimmune Myocarditis.

Currently available imaging techniques have limited specificity for the detection of active myocardial inflammation. Aluminum F-labeled 1,4,7-triazacyclononane--triacetic acid conjugated folate (F-FOL) is a PET tracer targeting folate receptor β (FR-β), which is expressed on activated macrophages at sites of inflammation. We evaluated F-FOL PET for the detection of myocardial inflammation in rats with autoimmune myocarditis and studied the expression of FR-β in human cardiac sarcoidosis specimens.

(2S, 4R)-4-[F]Fluoroglutamine for In vivo PET Imaging of Glioma Xenografts in Mice: an Evaluation of Multiple Pharmacokinetic Models.

Purpose: The glutamine analogue (2S, 4R)-4-[F]fluoroglutamine ([F]FGln) was investigated to further characterize its pharmacokinetics and acquire in vivo positron emission tomography (PET) images of separate orthotopic and subcutaneous glioma xenografts in mice.

Procedures: [F]FGln was synthesized at a high radiochemical purity as analyzed by high-performance liquid chromatography. An orthotopic model was created by injecting luciferase-expressing patient-derived BT3 glioma cells into the right hemisphere of BALB/cOlaHsd-Foxn1 mouse brains (tumor growth monitored via in vivo bioluminescence), the subcutaneous model by injecting rat BT4C glioma cells into the flank and neck regions of Foxn1 mice.

Folate receptor-targeted positron emission tomography of experimental autoimmune encephalomyelitis in rats.

Background: Folate receptor-β (FR-β) is a cell surface receptor that is significantly upregulated on activated macrophages during inflammation and provides a potential target for folate-based therapeutic and diagnostic agents. FR-β expression in central nervous system inflammation remains relatively unexplored. Therefore, we used focally induced acute and chronic phases of experimental autoimmune encephalomyelitis (EAE) to study patterns of FR-β expression and evaluated its potential as an in vivo imaging target.

Aluminum fluoride-18 labeled folate enables in vivo detection of atherosclerotic plaque inflammation by positron emission tomography.

Inflammation plays an important role in the development of atherosclerosis and its complications. Because the folate receptor β (FR-β) is selectively expressed on macrophages, an FR targeted imaging agent could be useful for assessment of atherosclerotic inflammation. We investigated aluminum fluoride-18-labeled 1,4,7-triazacyclononane-1,4,7-triacetic acid conjugated folate (F-FOL) for the detection of atherosclerotic plaque inflammation.

Vascular adhesion protein-1 is actively involved in the development of inflammatory lesions in rat models of multiple sclerosis.

Background: Vascular adhesion protein-1 (VAP-1) is an inflammation-inducible endothelial cell molecule and primary amine oxidase that mediates leukocyte entry to sites of inflammation. However, there is limited knowledge of the inflammation-related expression of VAP-1 in the central nervous system (CNS). Therefore, we investigated the expression of VAP-1 within the CNS vasculature in two focal rat models of experimental autoimmune encephalomyelitis (EAE) mimicking multiple sclerosis (MS).

Metformin treatment significantly enhances intestinal glucose uptake in patients with type 2 diabetes: Results from a randomized clinical trial.

Aims: Metformin therapy is associated with diffuse intestinal F-fluoro-deoxyglucose (FDG) accumulation in clinical diagnostics using routine FDG-PET imaging. We aimed to study whether metformin induced glucose uptake in intestine is associated with the improved glycaemic control in patients with type 2 diabetes. Therefore, we compared the effects of metformin and rosiglitazone on intestinal glucose metabolism in patients with type 2 diabetes in a randomized placebo controlled clinical trial, and further, to understand the underlying mechanism, evaluated the effect of metformin in rats.

Effects of atorvastatin and diet interventions on atherosclerotic plaque inflammation and [F]FDG uptake in LdlrApob mice.

Background And Aims: Uptake of the positron emission tomography (PET) tracer 2-deoxy-2-[F]-fluoro-d- glucose ([F]FDG) into macrophages is a sensitive marker of inflammation in atherosclerosis. To assess the anti-inflammatory effects of statins, we studied whether atorvastatin therapy reduces aortic [F]FDG uptake in hypercholesterolemic mice deficient in low-density lipoprotein receptor (Ldlr), and expressing only apolipoprotein B-100 (LdlrApob).

Methods: Thirty-six LdlrApob mice were fed a high-fat diet (HFD) for 12 weeks and then allocated to receive a HFD (n = 13), chow diet (Chow, n = 12), or HFD with added atorvastatin (HFD + A, n = 11), for another 12 weeks.

Synthesis and In Vivo PET Imaging of Hyaluronan Conjugates of Oligonucleotides.

Synthesis for (68)Ga-labeled 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA)-chelated oligonucleotide hyaluronan (HA) tetra- and hexasaccharide conjugates is described. A solid-supported technique is used to introduce NOTA-chelator into the 3'-terminus of oligonucleotides and a copper-free strain promoted azide alkyne cycloaddition (SPAAC) to HA/oligonucleotide conjugation. Protecting group manipulation, required for the HA-moieties, is carried out after the SPAAC-conjugation.

Comparison of Somatostatin Receptor 2-Targeting PET Tracers in the Detection of Mouse Atherosclerotic Plaques.

Purpose: Rupture-prone atherosclerotic plaques are characterized by accumulation of macrophages, which have shown to express somatostatin type 2 receptors. We aimed to investigate whether somatostatin receptor-targeting positron emission tomography (PET) tracers, [(68)Ga]DOTANOC, [(18)F]FDR-NOC, and [(68)Ga]DOTATATE, can detect inflamed atherosclerotic plaques.

Procedures: Atherosclerotic IGF-II/LDLR(-/-)ApoB(100/100) mice were studied in vivo and ex vivo for tracer uptake into atherosclerotic plaques.