A5089624017- Medical Imaging Techniques and Applications
- Neuroscience and Neuropharmacology Research
- Receptor Mechanisms and Signaling
- Neurotransmitter Receptor Influence on Behavior
- Epilepsy research and treatment
- Glioma Diagnosis and Treatment
- Nicotinic Acetylcholine Receptors Study
- Advanced MRI Techniques and Applications
- Alzheimer's disease research and treatments
- Functional Brain Connectivity Studies
- Stress Responses and Cortisol
- Phosphodiesterase function and regulation
- Cannabis and Cannabinoid Research
- Neuropeptides and Animal Physiology
- Neurological Disease Mechanisms and Treatments
- Pancreatic function and diabetes
- Cancer, Hypoxia, and Metabolism
- Radiopharmaceutical Chemistry and Applications
- Pharmacological Receptor Mechanisms and Effects
- Neuroscience of respiration and sleep
- Lung Cancer Treatments and Mutations
- Smoking Behavior and Cessation
- Schizophrenia research and treatment
- S100 Proteins and Annexins
- Prostate Cancer Treatment and Research
Yale University
2014-2024
Yale Cancer Center
2013-2024
University of New Haven
2014
Itron (United States)
2013
Synaptic loss is well established as the major structural correlate of cognitive impairment in Alzheimer disease (AD). The ability to measure synaptic density vivo could accelerate development disease-modifying treatments for AD. vesicle glycoprotein 2A an essential membrane protein expressed virtually all synapses and serve a suitable target density.To compare hippocampal (SV2A) binding participants with AD cognitively normal using positron emission tomographic (PET) imaging.This...
The synaptic vesicle glycoprotein 2A (SV2A) is found in secretory vesicles neurons and endocrine cells. PET with a selective SV2A radiotracer will allow characterization of drugs that modulate (e.g., antiepileptic drugs) potentially could be biomarker density neurodegenerative disorders). Here we describe the synthesis <sup>11</sup>C-UCB-J ((<i>R</i>)-1-((3-(<sup>11</sup>C-methyl-<sup>11</sup>C)pyridin-4-yl)methyl)-4-(3,4,5-trifluorophenyl)pyrrolidin-2-one) nonhuman primates, including...
PET imaging of synaptic vesicle glycoprotein 2A allows for noninvasive quantification synapses. This first-in-human study aimed to evaluate the kinetics, test-retest reproducibility, and extent specific binding a recently developed ligand, (
Detecting changes in receptor binding at the metabotropic glutamate 5 (mGluR5) with PET allosteric antagonist, [¹¹C]ABP688, may be valuable for studying dysfunctional transmission associated psychiatric illnesses. This study was designed to validate findings of a recent pilot baboons which reported significant global decrease from baseline [¹¹C]ABP688 after increasing endogenous 50 mg/kg N-acetylcysteine (NAC), no change test retest. In rhesus monkeys (n = 5), paired scans were performed on...
<sup>11</sup>C-LY2795050 is a new antagonist PET radioligand for the κ opioid receptor (KOR). In this study, we assessed reproducibility of binding parameters in healthy human subjects. <b>Methods:</b> Sixteen subjects (11 men and 5 women) underwent 2 separate 90-min scans with arterial input function plasma free fraction (<i>f</i><sub>P</sub>) measurements. The 2-tissue-compartment model multilinear analysis-1 were applied to calculate outcome measures 14 brain regions: distribution volume...
Naltrexone is a nonselective opioid receptor antagonist used as treatment for alcohol use disorder. However, only modest clinical effects have been observed, possibly because of limited knowledge about the biological variables affecting efficacy naltrexone. We investigated potential role kappa (KOR) in therapeutic effect naltrexone.A total 48 non-treatment-seeking heavy drinkers (16 women) who met DSM-IV criteria dependence participated two drinking paradigms (ADPs) separated by week...
<sup>11</sup>C-LY2795050 is a novel κ-selective antagonist PET tracer. The in vitro binding affinities (<i>K</i><sub>i</sub>) of LY2795050 at the κ-opioid (KOR) and μ-opioid (MOR) receptors are 0.72 25.8 nM, respectively. Thus, KOR/MOR selectivity about 36:1. Our goal this study was to determine vivo new KOR tracer monkey. <b>Methods:</b> To estimate <i>ED</i><sub>50</sub> value (dose compound [or drug] that gives 50% occupancy target receptor) MOR sites, 2 series blocking experiments were...
Type 1 diabetes mellitus (T1DM) is characterized by a loss of β-cells in the islets Langerhans pancreas and subsequent deficient insulin secretion response to hyperglycemia. Development an vivo test measure β-cell mass (BCM) would greatly enhance ability track therapies. neurologic tissues have common cellular receptors transporters, therefore, we screened brain radioligands for their identify β-cells. <b>Methods:</b> We examined gene atlas endocrine receptor targets cross-referenced these...
Type 1 diabetes mellitus (T1DM) has traditionally been characterized by a complete destruction of β-cell mass (BCM); however, there is growing evidence possible residual BCM present in T1DM. Given the absence vivo tools to measure BCM, routine clinical measures function (e.g., C-peptide release) may not reflect BCM. We previously demonstrated potential utility PET imaging with dopamine D<sub>2</sub> and D<sub>3</sub> receptor agonist...
The lysophosphatidic acid receptor type 1 (LPA1) is of 6 known receptors the extracellular signaling molecule acid. It mediates effects such as cell proliferation, migration, and differentiation. In lung, LPA1 involved in pathways leading, after lung tissue injury, to pulmonary fibrosis instead normal healing, by mediating fibroblast recruitment vascular leakage. Thus, a PET radiotracer may be useful for studying or developing LPA1-targeting drugs. We developed evaluated 11C-BMT-136088...
[11C]MP-10 is a potent and specific PET tracer previously shown to be suitable for imaging the phosphodiesterase 10A (PDE10A) in baboons with reversible kinetics high binding. However, another report indicated that displayed seemingly irreversible rhesus monkeys, potentially due presence of radiolabeled metabolite capable penetrating blood-brain-barrier (BBB) into brain. This study was designed address discrepancies between species by re-evaluating vivo monkey baseline scans assess tissue...
The M<sub>1</sub> muscarinic acetylcholine receptor (mAChR) plays an important role in learning and memory, therefore is a target for development of drugs treatment cognitive impairments Alzheimer disease schizophrenia. availability M<sub>1</sub>-selective radiotracers PET will help developing therapeutic agents by providing imaging tool assessment drug dose-receptor occupancy relationship. Here we report the synthesis evaluation <sup>11</sup>C-LSN3172176 (ethyl...
[ 11 C]AFM, or C]2-[2-(dimethylaminomethyl)phenylthio]-5-fluoromethylphenylamine, is a new positron emission tomography (PET) radioligand with high affinity and selectivity for the serotonin transporter (SERT). The purpose of this study was to determine most appropriate kinetic model quantify C]AFM binding in healthy human brain. Positron data arterial input functions were acquired from 10 subjects. Compartmental modeling multilinear analysis-1(MA1) method tested using functions. one-tissue...
The enzyme phosphodiesterase 2A (PF-05270430) is a potential target for development of novel therapeutic agents the treatment cognitive impairments. goal present study was to evaluate PDE2A ligand <sup>18</sup>F-PF-05270430, 4-(3-fluoroazetidin-1-yl)-7-methyl-5-(1-methyl-5-(4-(trifluoromethyl)phenyl)-1H-pyrazol-4-yl)imidazo[1,5-f][1,2,4]triazine, in nonhuman primates. <b>Methods:</b><sup>18</sup>F-PF-05270430 radiolabeled by 2 methods via nucleophilic substitution its tosylate precursor....
Serotonergic neurotransmission plays a key role in the pathophysiology and treatment of various neuropsychiatric diseases. The purpose this study was to investigate changes serotonergic after acute tryptophan depletion (ATD) using positron emission tomography (PET) with [11 C]P943, 5-HT1B receptor radioligand previously shown be sensitive 5-HT. Five healthy subjects were scanned on high resolution PET scanner twice same day, before approximately 5 hours ingesting capsules containing an amino...
BACKGROUNDInvestigations of stress dysregulation in posttraumatic disorder (PTSD) have focused on peripheral cortisol, but none examined cortisol the human brain. This study used positron emission tomography (PET) to image 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), a cortisol-producing enzyme, as putative brain marker PTSD.METHODSSixteen individuals with PTSD and 17 healthy, trauma-exposed controls (TCs) underwent PET imaging [18F]AS2471907, radioligand for...
11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) catalyzes enzymatic conversion of cortisone into the stress hormone cortisol. This first-in-human brain imaging study characterizes kinetic modeling and test-retest reproducibility [18F]AS2471907, a novel PET radiotracer for 11β-HSD1. Eight individuals underwent one 180-min (n = 4) or two 240-min [18F]AS2471907 scans (12 total) acquired on high-resolution research tomograph (HRRT) scanner with arterial blood sampling. Imaging data were...
Abstract [18F]FE-PE2I PET is a promising alternative to single positron emission computed tomography–based dopamine transporter (DAT) imaging in Parkinson’s disease. While the excellent discriminative power of has been established, so far only one study reported meaningful associations between motor severity scores and DAT availability. In this study, we use high-resolution (∼3 mm isotropic) provide an independent validation for clinical correlates separate cross-sectional (28 participants...
Brain cannabinoid 1 receptors (CB1Rs) contribute importantly to the regulation of autonomic tone, appetite, mood and cognition. Inconsistent results have been reported from positron emission tomography (PET) studies using different radioligands examine relationships between age, gender body mass index (BMI) CB1R availability in healthy individuals. In this study, we examined these variables 58 individuals (age range: 18-55 years; 44 male; BMI=27.01±5.56), largest cohort subjects studied date...