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.

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.

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.

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.

Imaging of [60]Fullerene-Based Molecular Spherical Nucleic Acids by Positron Emission Tomography.

F-Labeled [60]fullerene-based molecular spherical nucleic acids (MSNAs), consisting of a human epidermal growth factor receptor 2 (HER2) mRNA antisense oligonucleotide sequence with a native phosphodiester and phosphorothioate backbone, were synthesized, site-specifically labeled with a positron emitting fluorine-18 and intravenously administrated via tail vein to HER2 expressing HCC1954 tumor-bearing mice. The biodistribution of the MSNAs was monitored by positron emission tomography/computed tomography (PET/CT) imaging. MSNA with a native phosphodiester backbone (MSNA-PO) was prone to rapid nuclease-mediated degradation, whereas the corresponding phosphorothioate analogue (MSNA-PS) with improved enzymatic stability showed an interesting biodistribution profile .

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.

Aluminum Fluoride-18 Labeled Mannosylated Dextran: Radiosynthesis and Initial Preclinical Positron Emission Tomography Studies.

Purpose: In addition to being expressed on liver sinusoidal endothelial cells, mannose receptors are also found on antigen-presenting cells, including macrophages, which are mainly involved in the inflammation process. Dextran derivatives of various sizes containing cysteine and mannose moieties have previously been labeled with Tc and used for single-photon emission computed tomography imaging of sentinel lymph nodes. In this study, we radiolabeled 21.

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.

[Ga]Ga-DOTA-Siglec-9 Detects Pharmacodynamic Changes of FAP-Targeted IL2 Variant Immunotherapy in B16-FAP Melanoma Mice.

Vascular adhesion protein-1 (VAP-1) is an inflammation-inducible adhesion molecule, which supports contact between leukocytes and inflamed endothelium. There is evidence that VAP-1 is involved in the recruitment of leukocytes to melanoma tumors. Interleukin-2 (IL-2)-based immunotherapy is an efficient therapy that promotes immune system activity against cancers but is associated with toxicity.

Development of [F]AmBF Tetrazine for Radiolabeling of Peptides: Preclinical Evaluation and PET Imaging of [F]AmBF-PEG-Tyr-Octreotide in an AR42J Pancreatic Carcinoma Model.

Radiolabeled peptides have emerged as highly specific agents for targeting receptors expressed in tumors for therapeutic and diagnostic purposes. Peptides developed for positron emission tomography (PET) are typically radiolabeled using prosthetic groups or bifunctional chelators for fast "kit-like" incorporation of the radionuclide into the structure. A novel [F]alkylammoniomethyltrifluoroborate ([F]AmBF) tetrazine (Tz), [F]AmBF-Tz, was developed for the [F]fluorination of -cyclooctene (TCO)-modified biomolecules using Tyr-octreotides (TOCs) as model peptides.

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.

Statistical Evaluation of Different Mathematical Models for Diffusion Weighted Imaging of Prostate Cancer Xenografts in Mice.

Purpose: To evaluate fitting quality and repeatability of four mathematical models for diffusion weighted imaging (DWI) during tumor progression in mouse xenograft model of prostate cancer.

Methods: Human prostate cancer cells (PC-3) were implanted subcutaneously in right hind limbs of 11 immunodeficient mice. Tumor growth was followed by weekly DWI examinations using a 7T MR scanner.

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.

Docetaxel chemotherapy response in PC3 prostate cancer mouse model detected by rotating frame relaxations and water diffusion.

MRI is a common method of prostate cancer diagnosis. Several MRI-derived markers, including the apparent diffusion coefficient (ADC) based on diffusion-weighted imaging, have been shown to provide values for prostate cancer detection and characterization. The hypothesis of the study was that docetaxel chemotherapy response could be picked up earlier with rotating frame relaxation times T and T than with the continuous wave T , adiabatic T , adiabatic T , T , T or water ADC.

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.

The circadian gene Cryptochrome 2 influences stress-induced brain activity and depressive-like behavior in mice.

Cryptochrome 2 (Cry2) is a core clock gene important for circadian regulation. It has also been associated with anxiety and depressive-like behaviors in mice, but the previous findings have been conflicting in terms of the direction of the effect. To begin to elucidate the molecular mechanisms of this association, we carried out behavioral testing, PET imaging, and gene expression analysis of Cry2 and Cry2 mice.

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.

Hydroxysteroid (17β) dehydrogenase 12 is essential for metabolic homeostasis in adult mice.

Hydroxysteroid 17β dehydrogenase 12 (HSD17B12) is suggested to be involved in the elongation of very long chain fatty acids. Previously, we have shown a pivotal role for the enzyme during mouse development. In the present study we generated a conditional knockout (HSD17B12cKO) mouse model by breeding mice homozygous for a floxed allele with mice expressing the tamoxifen-inducible Cre recombinase at the ROSA26 locus.