A5057843592- Receptor Mechanisms and Signaling
- Neuroscience and Neuropharmacology Research
- Medical Imaging Techniques and Applications
- Neurotransmitter Receptor Influence on Behavior
- Pharmacological Receptor Mechanisms and Effects
- Radiopharmaceutical Chemistry and Applications
- Forensic Toxicology and Drug Analysis
- Neuropeptides and Animal Physiology
- Renin-Angiotensin System Studies
- Eicosanoids and Hypertension Pharmacology
- Nitric Oxide and Endothelin Effects
- Nicotinic Acetylcholine Receptors Study
- Advanced MRI Techniques and Applications
- Hormonal Regulation and Hypertension
- Parkinson's Disease Mechanisms and Treatments
- Cannabis and Cannabinoid Research
- Synthesis and Biological Evaluation
- Cholinesterase and Neurodegenerative Diseases
- Adenosine and Purinergic Signaling
- Ion channel regulation and function
- MRI in cancer diagnosis
- Electron Spin Resonance Studies
- Chemical Synthesis and Analysis
- Neuroinflammation and Neurodegeneration Mechanisms
- Renal and Vascular Pathologies
Johns Hopkins University
2014-2024
Johns Hopkins Medicine
2006-2022
Society of Nuclear Medicine and Molecular Imaging
2021
University of Baltimore
2019
Memorial Sloan Kettering Cancer Center
2019
Johns Hopkins Hospital
2011
Imaging Center
1998
National Institute on Drug Abuse
1998
Villanova University
1995
The chemogenetic technology DREADD (designer receptors exclusively activated by designer drugs) is widely used for remote manipulation of neuronal activity in freely moving animals. posits the use "designer receptors," which are drug" clozapine N-oxide (CNO). Nevertheless, vivo mechanism action CNO at DREADDs has never been confirmed. does not enter brain after systemic drug injections and shows low affinity DREADDs. Clozapine, to rapidly converts vivo, high potency. Upon injections,...
Significance [ 11 C]CPPC [5-cyano- N -(4-(4-[ C]methylpiperazin-1-yl)-2-(piperidin-1-yl)phenyl)furan-2-carboxamide] is a PET radiotracer specific for CSF1R, microglia-specific marker. This compound can be used as noninvasive tool imaging of reactive microglia, disease-associated microglia and their contribution to neuroinflammation in vivo. Neuroinflammation posited an underlying pathogenic feature wide variety neuropsychiatric disorders. may also study specifically the immune environment...
The present study sought to determine whether doses of methamphetamine in the range those used recreationally by humans produce brain dopamine (DA) neurotoxicity baboons and ascertain positron emission tomography (PET) imaging with DA transporter (DAT) ligand [ 11 C]WIN-35,428 ([ C]2β-carbomethoxy-3β-(4-fluorophenyl)-tropane) could be detect methamphetamine-induced DAT loss living primates. Baboons were treated saline ( n = 3) or one three [0.5 mg/kg 2); 1 2 3)], each which was given...
Abstract This paper presents the first Positron Emission Tomography (PET) images of serotonin (5‐hydroxytryptamine, 5‐HT) transporter in living human brain. PET imaging was performed three healthy subjects after administration [ 11 C](+)McN5652 (the (+) enantiomer trans‐l,2,3,5,6,10β‐hexahydro‐6‐[4‐(methylthio) phenyl]pyrrolo‐[2,1‐a] ‐isoquinoline), a radioligand previously shown to selectively label 5‐HT vivo mammalian (mouse and baboon) To demonstrate specificity binding, additional were...
<h3>Background</h3> Little is known about serotonin neurons in Parkinson disease (PD). <h3>Objective</h3> To study the system PD with positron emission tomography, using transporter radioligand [<sup>11</sup>C](+)McN5652. <h3>Design and Patients</h3> We measured density of [<sup>11</sup>C]WIN35 428–labeled dopamine transporters striatum 13 adults age- sex-matched controls. assess effects possible differences blood flow or brain atrophy, we also regional cerebral size regions interest for...
The present study evaluated short- and long-term effects of MDMA (3,4-methylenedioxymethamphetamine) in the baboon brain using PET [11C](+)McN 5652, a potent 5-HT transporter ligand, as well [11C]RTI-55, cocaine derivative which labels both dopamine transporters. Following baseline scans with [11C](+)McN5652, [11C](−)McN5652 (the inactive enantiomer active [11C](+)McN5652) was treated (5 mg/kg, s.c., twice daily for four consecutive days). studies at 13, 19, 40 days post-MDMA revealed...
PET reveals spatially heterogeneous rifampin brain penetration, which decreases rapidly with treatment during tuberculous meningitis.
MAO is one of the enzymes involved in metabolism potent biogenic amines such as l-epinephrine, l-norepinephrine, serotonin, tyramine, and dopamine.<sup>4</sup>After administration inhibitors, it believed that there an increase tissue levels l-epinephrine l-norepinephrine. Tyramine may act a pressor substance normally degraded by MAO, or provoke release stored catechol amines.<sup>5</sup>As contrasted with pheochromocytoma, urinary 3-methoxy, 4-hydroxymandelic acid determinations have been...
Aggregates of tau and beta amyloid (Aβ) plaques constitute the histopathological hallmarks Alzheimer's disease are prominent targets for novel therapeutics as well biomarkers diagnostic in vivo imaging. In recent years much attention has been devoted to discovery development new PET tracers image aggregates living human brain. Access a selective tracer quantify represents unique tool support any therapeutic agent targeting pathological forms tau. The objective study described herein was...
Abstract The involvement of opioid neurotransmitter systems in seizure mechanisms is well documented. In previous positron emission tomography (PET) studies patients with unilateral temporal lobe epilepsy, we have found evidence for differential regulation the opioid‐receptor subtypes. present study extends our observations to δ‐opioid receptors by using δ‐receptor‐selective antagonist [ 11 C]methylnatrindole ([ C]MeNTI). Paired measurements δ‐ and μ‐opioid receptor binding metabolic...
The pathophysiology of post-treatment Lyme disease syndrome (PTLDS) may be linked to overactive immunity including aberrant activity the brain's resident immune cells, microglia. Here we used [11C]DPA-713 and positron emission tomography quantify 18 kDa translocator protein, a marker activated microglia or reactive astrocytes, in brains patients with symptoms any duration compared healthy controls. Genotyping for TSPO rs6971 polymorphism was completed, individuals rare, low affinity binding...
The impulse response function of a radioligand is the most fundamental way to describe its pharmacokinetics and assess tissue uptake retention pattern. This study investigates [11C](+)McN5652, used for positron emission tomography (PET) imaging serotonin transporter (SERT) in brain. Dynamic PET studies were performed eight healthy volunteers injected with [11C](+)McN5652 subsequently pharmacologically inactive enantiomer [11C](-)McN5652. was calculated by deconvolution analysis regional...
Recently, we have developed the positron emitting radiotracer N1′-([11C]methyl)naltrindole ([11C]MeNTI) and demonstrated its high selectivity for δ opioid receptors in mouse brain [Lever et al. (1992) Eur. J. Pharmacol., 216:449-450]. In present study, examined of [11C]MeNTI receptor human brain, using emission tomography (PET). The regional kinetics distribution as well pharmacology confirmed brain. First, are accordance with density receptor. Rapid washout receptor-poor areas prolonged...
The renin–angiotensin system (RAS) mediates proapoptotic, profibrotic, and proinflammatory processes in maladaptive conditions. Activation after myocardial infarction may initialize promote cardiac remodeling. Using a novel positron-emitting ligand, we sought to determine the presence time course of regional upregulation angiotensin II type 1 receptor (AT1R) blocking efficacy various anti-RAS agents. <b>Methods:</b> In male Wistar rats (<i>n</i> = 31), ischemia–reperfusion damage was induced...
The in vivo brain regional distribution of 2-[18F]fluoro-A-85380, a novel tracer for positron emission tomographic (PET) studies, followed the densities nAChRs reported literature. Evidence binding to and high specificity was demonstrated by inhibition with nAChR selective ligands as well unlabeled 2-fluoro-A-85380. A preliminary toxicology study 2-fluoro-A-85380 showed relatively low biological effect. 2-[18F]Fluoro-A-85380 holds promise useful radiotracer imaging PET.
Four halogen-substituted analogues of N-methylepibatidine, a nicotinic acetylcholine receptor (nAChR) ligand, were synthesized. They (+/-)-exo-N-methyl-2-(2-halogeno-5-pyridyl)-7-azabicyclo[2. 2.1]heptanes, where halogeno = F (1a), Cl (2a), Br (3a), I (4a). (+/-)-N-Ethylepibatidine (2b) also was The compounds 1a, 2a, 3a, and 4a their corresponding normethyl 1, 2, 3, 4 inhibited the in vitro binding [3H]epibatidine to nAChRs similar degree, with affinities 27-50 pM range. affinity...
The radiochemical synthesis of 2-[18F]fluoro-3-(2(S)-azetidinylmethoxy)pyridine (2-[18F]A-85380, [18F]1) was accomplished by Kryptofix® 222 assisted nucleophilic no-carrier-added [18F]fluorination 2-iodo-3((1-tert-butoxycarbonyl-2(S)-azetidinyl)methoxy)pyridine, 2 followed acidic deprotection. average yield 10% and the specific radioactivity 1050 mCi/μmol, calculated at end-of-synthesis (EOS). © 1998 John Wiley & Sons, Ltd.