Ultra-high-field pharmacological functional MRI of dopamine D1 receptor-related interventions in anesthetized rats.

The dopamine D1 receptor (D1R) is associated with schizophrenia, Parkinson's disease, and attention deficit hyperactivity disorder. Although the receptor is considered a therapeutic target for these diseases, its neurophysiological function has not been fully elucidated. Pharmacological functional MRI (phfMRI) has been used to evaluate regional brain hemodynamic changes induced by neurovascular coupling resulting from pharmacological interventions, thus phfMRI studies can be used to help understand the neurophysiological function of specific receptors.

Anatomical variability, multi-modal coordinate systems, and precision targeting in the marmoset brain.

Localising accurate brain regions needs careful evaluation in each experimental species due to their individual variability. However, the function and connectivity of brain areas is commonly studied using a single-subject cranial landmark-based stereotactic atlas in animal neuroscience. Here, we address this issue in a small primate, the common marmoset, which is increasingly widely used in systems neuroscience.

Towards HCP-Style macaque connectomes: 24-Channel 3T multi-array coil, MRI sequences and preprocessing.

Macaque monkeys are an important animal model where invasive investigations can lead to a better understanding of the cortical organization of primates including humans. However, the tools and methods for noninvasive image acquisition (e.g.

A Novel Phosphodiesterase 1 Inhibitor DSR-141562 Exhibits Efficacies in Animal Models for Positive, Negative, and Cognitive Symptoms Associated with Schizophrenia.

In our drug discovery program, we identified a novel orally available and brain-penetrant phosphodiesterase (PDE) 1 inhibitor, 3-methyl-7-(tetrahydro-2-pyran-4-yl)-2-{[-4-(trifluoromethyl)cyclohexyl]-methoxy}imidazo[5,1-][1,2,4]triazin-4(3)-one (DSR-141562). In the present study, we characterized the preclinical profile of DSR-141562. This compound has preferential selectivity for predominantly brain-expressed PDE1B over other PDE1 family members, and high selectivity for the PDE1 family over other PDE families and 65 other tested biologic targets.

A novel Tungsten-based fiducial marker for multi-modal brain imaging.

Background: Multi-modal brain image registration is a prerequisite for accurate mapping of brain structure and function in neuroscience. Image registration is commonly performed using automated software; however, its accuracy decreases when images differ in modality, contrast, uniformity, and resolution. This limitation could be overcome by using an external reference point; however, high-contrast agents in multi-modal imaging have not been previously reported.

Comparison of I- and In-labeled peptide probes for in vivo detection of oxidized low-density lipoprotein in atherosclerotic plaques.

Objective: Oxidized low-density lipoprotein (OxLDL) plays a pivotal role in atherosclerotic plaque destabilization, which suggests its potential as a nuclear medical imaging target. We previously developed radioiodinated I-AHP7, a peptide probe carrying a 7-residue sequence from the OxLDL-binding protein Asp-hemolysin, for specific OxLDL imaging. Although I-AHP7 recognized OxLDL, it had low stability.

Radiofluorinated probe for PET imaging of fatty acid binding protein 4 in cancer.

Introduction: Cancer-associated adipocytes metabolically interact with adjacent cancer cells to promote tumor proliferation and metastasis. Fatty acid binding protein 4 (FABP4) participates in this interaction, and is gathering attention as a therapeutic and diagnostic target. Positron emission tomography (PET) is a useful diagnostic method that enables noninvasive in vivo quantitative imaging of biofunctional molecules with probes labeled with positron-emitting radioisotopes.

Development of a radioiodinated triazolopyrimidine probe for nuclear medical imaging of fatty acid binding protein 4.

Fatty acid binding protein 4 (FABP4) is the most well-characterized FABP isoform. FABP4 regulates inflammatory pathways in adipocytes and macrophages and is involved in both inflammatory diseases and tumor formation. FABP4 expression was recently reported for glioblastoma, where it may participate in disease malignancy.

Radioiodinated peptide probe for selective detection of oxidized low density lipoprotein in atherosclerotic plaques.

Introduction: Despite the significant effort in developing radioprobes for atherosclerosis, few have low molecular weight. Oxidized LDL (OxLDL), a highly proinflammatory and proatherogenic factor that is abundant in atherosclerotic plaques, plays a pivotal role in plaque destabilization, which makes OxLDL a relevant probe target. We developed a radioiodinated short peptide, AHP7, as a low molecular weight probe for specific OxLDL imaging and evaluated its utility using myocardial infarction-prone Watanabe heritable hyperlipidemic rabbits (WHHLMI).

Tissue factor detection for selectively discriminating unstable plaques in an atherosclerotic rabbit model.

Unlabelled: Tissue factor (TF), a transmembrane glycoprotein that acts as an essential cofactor to factor VII/VIIa, initiates the exogenous blood coagulation cascade leading to thrombin generation and subsequent thrombus formation in vivo. TF expression is closely related to plaque vulnerability, and high TF expression is shown in macrophage-rich atheromatous lesions, making TF a potential target for detecting atheromatous lesions in vivo. Thus, we prepared (99m)Tc-labeled anti-TF-monoclonal antibody (TF-mAb) IgG as a molecular probe and evaluated its usefulness to achieve TF-specific imaging using myocardial infarction-prone Watanabe heritable hyperlipidemic (WHHLMI) rabbits.

Imaging with radiolabelled anti-membrane type 1 matrix metalloproteinase (MT1-MMP) antibody: potentials for characterizing atherosclerotic plaques.

Purpose: Membrane type 1 matrix metalloproteinase (MT1-MMP) activates pro-MMP-2 and pro-MMP-13 to their active forms and plays important roles in the destabilization of atherosclerotic plaques. This study sought to determine the usefulness of (99m)Tc-labelled monoclonal antibody (mAb), recognizing MT1-MMP, for imaging atherosclerosis in a rabbit model (WHHLMI rabbits).

Methods: Anti-MT1-MMP monoclonal IgG(3) and negative control IgG(3) were radiolabelled with (99m)Tc after derivatization with 6-hydrazinonicotinic acid (HYNIC) to yield (99m)Tc-MT1-MMP mAb and (99m)Tc-IgG(3), respectively.