Imaging the translocator protein 18 kDa within cognitive control and declarative memory circuits in virally suppressed people with HIV.

Objectives: Virally suppressed people with HIV (VS-PWH) show heterogeneity in patterns of cognitive dysfunction. To better understand the relationship between the neuroimmune response and cognition, we used PET to image the translocator protein 18 kDa (TSPO). The study examined HIV-serostatus differences in TSPO as well as associations between regional TSPO and select cognitive processes defined using the Research Domain Criteria (RDoC) framework.

Imaging Brain Injury in Former National Football League Players.

Importance: Pilot studies that involved early imaging of the 18 kDa translocator protein (TSPO) using positron emission tomography (PET) indicated high levels of TSPO in the brains of active or former National Football League (NFL) players. If validated further in larger studies, those findings may have implications for athletes involved in collision sport.

Objective: To test for higher TSPO that marks brain injury and repair in a relatively large, unique cohort of former NFL players compared with former elite, noncollision sport athletes.

First-in-human imaging using [C]MDTC: a radiotracer targeting the cannabinoid receptor type 2.

Purpose: We report findings from the first-in-human study of [C]MDTC, a radiotracer developed to image the cannabinoid receptor type 2 (CB2R) with positron emission tomography (PET).

Methods: Ten healthy adults were imaged according to a 90-min dynamic PET protocol after bolus intravenous injection of [C]MDTC. Five participants also completed a second [C]MDTC PET scan to assess test-retest reproducibility of receptor-binding outcomes.

Molecular imaging of beta-amyloid deposition in late-life depression.

Late-life depression (LLD) is associated with an increased risk of all-cause dementia and may involve Alzheimer's disease pathology. Twenty-one LLD patients who met the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, criteria for a current major depressive episode and 21 healthy controls underwent clinical and neuropsychological assessments, magnetic resonance imaging to measure gray matter volumes, and high-resolution positron emission tomography to measure beta-amyloid (Aβ) deposition. Clinical and neuropsychological assessments were repeated after 10-12 weeks of Citalopram or Sertraline treatment (LLD patients only).

Molecular imaging of the serotonin transporter availability and occupancy by antidepressant treatment in late-life depression.

Patients with late-life depression (LLD) have a more variable response to pharmacotherapy relative to patients with mid-life depression. Degeneration of the serotonergic system and lower occupancy of the initial target for antidepressant medications, the serotonin transporter (5-HTT), may contribute to variability in treatment response. The focus of this study was to test the hypotheses that lower cortical and limbic serotonin transporter (5-HTT) availability in LLD patients relative to controls and less 5-HTT occupancy by antidepressant medications would be associated with less improvement in mood and cognition with treatment in LLD patients.

F-labeled radiotracers for in vivo imaging of DREADD with positron emission tomography.

Designer Receptors Exclusively Activated by Designer Drugs (DREADD) are a preclinical chemogenetic approach with clinical potential for various disorders. In vivo visualization of DREADDs has been achieved with positron emission tomography (PET) using C radiotracers. The objective of this study was to develop DREADD radiotracers labeled with F for a longer isotope half-life.

Correction to: Osteopontin/secreted phosphoprotein-1 behaves as a molecular brake regulating the neuroinflammatory response to chronic viral infection.

An amendment to this paper has been published and can be accessed via the original article.

Osteopontin/secreted phosphoprotein-1 behaves as a molecular brake regulating the neuroinflammatory response to chronic viral infection.

Background: Osteopontin (OPN) as a secreted signaling protein is dramatically induced in response to cellular injury and neurodegeneration. Microglial inflammatory responses in the brain are tightly associated with the neuropathologic hallmarks of neurodegenerative disease, but understanding of the molecular mechanisms remains in several contexts poorly understood.

Methods: Micro-positron emission tomography (PET) neuroimaging using radioligands to detect increased expression of the translocator protein (TSPO) receptor in the brain is a non-invasive tool used to track neuroinflammation in living mammals.

Radiosynthesis and validation of [5-cyano-N-(4-(4-[ C]methylpiperazin-1-yl)-2-(piperidin-1-yl)phenyl) furan-2-carboxamide] ([ C]CPPC), a PET radiotracer for imaging CSF1R, a microglia-specific marker.

In this practitioner protocol, the radiochemical synthesis of [ C]CPPC is described in detail, and a quality control summary of three validation productions is presented. The results indicate that the radiotracer product can be produced in good radiochemical yield (> 60 mCi (2.22 GBq) at end-of-synthesis (EOS)), at high specific activity (molar activity > 11,435 mCi/μmole (423 GBq/μmole) at EOS) and high chemical and radiochemical purity.

Effect of STN DBS on vesicular monoamine transporter 2 and glucose metabolism in Parkinson's disease.

Introduction: Deep brain stimulation (DBS) is an established treatment for Parkinson's Disease (PD). Despite the improvement of motor symptoms in most patients by sub-thalamic nucleus (STN) DBS and its widespread use, the neurobiological mechanisms are not completely understood. The objective of the present study was to elucidate the effects of subthalamic nucleus (STN) DBS in PD on the dopamine system and neural circuitry, employing high-resolution positron emission tomography (PET) imaging.

PET imaging of microglia by targeting macrophage colony-stimulating factor 1 receptor (CSF1R).

While neuroinflammation is an evolving concept and the cells involved and their functions are being defined, microglia are understood to be a key cellular mediator of brain injury and repair. The ability to measure microglial activity specifically and noninvasively would be a boon to the study of neuroinflammation, which is involved in a wide variety of neuropsychiatric disorders including traumatic brain injury, demyelinating disease, Alzheimer's disease (AD), and Parkinson's disease, among others. We have developed [C]CPPC [5-cyano--(4-(4-[C]methylpiperazin-1-yl)-2-(piperidin-1-yl)phenyl)furan-2-carboxamide], a positron-emitting, high-affinity ligand that is specific for the macrophage colony-stimulating factor 1 receptor (CSF1R), the expression of which is essentially restricted to microglia within brain.

Imaging glial activation in patients with post-treatment Lyme disease symptoms: a pilot study using [C]DPA-713 PET.

The pathophysiology of post-treatment Lyme disease syndrome (PTLDS) may be linked to overactive immunity including aberrant activity of the brain's resident immune cells, microglia. Here we used [C]DPA-713 and positron emission tomography to quantify the 18 kDa translocator protein, a marker of activated microglia or reactive astrocytes, in the brains of patients with post-treatment Lyme disease symptoms of any duration compared to healthy controls. Genotyping for the TSPO rs6971 polymorphism was completed, and individuals with the rare, low affinity binding genotype were excluded.

Noninvasive C-rifampin positron emission tomography reveals drug biodistribution in tuberculous meningitis.

Tuberculous meningitis (TBM) is a devastating form of tuberculosis (TB), and key TB antimicrobials, including rifampin, have restricted brain penetration. A lack of reliable data on intralesional drug biodistribution in infected tissues has limited pharmacokinetic (PK) modeling efforts to optimize TBM treatments. Current methods to measure intralesional drug distribution rely on tissue resection, which is difficult in humans and generally limited to a single time point even in animals.

Feasibility Evaluation of Myocardial Cannabinoid Type 1 Receptor Imaging in Obesity: A Translational Approach.

Objectives: The aim of this study was to evaluate the feasibility of targeted imaging of myocardial cannabinoid type 1 receptor (CB1-R) and its potential up-regulation in obese mice with translation to humans using [C]-OMAR and positron emission tomography (PET)/computed tomography (CT).

Background: Activation of myocardial CB1-R by endocannabinoids has been implicated in cardiac dysfunction in diabetic mice. Obesity may lead to an up-regulation of myocardial CB1-R, potentially providing a mechanistic link between obesity and the initiation and/or progression of cardiomyopathy.

Development of a radioligand for imaging V vasopressin receptors with PET.

A series of vasopressin receptor V ligands have been synthesized for positron emission tomography (PET) imaging. The lead compound (1S,5R)-1 ((4-(1H-indol-3-yl)-3-methoxyphenyl) ((1S,5R)-1,3,3-trimethyl-6-azabicyclo[3.2.

Chemogenetics revealed: DREADD occupancy and activation via converted clozapine.

The chemogenetic technology DREADD (designer receptors exclusively activated by designer drugs) is widely used for remote manipulation of neuronal activity in freely moving animals. DREADD technology posits the use of "designer receptors," which are exclusively activated by the "designer drug" clozapine N-oxide (CNO). Nevertheless, the in vivo mechanism of action of CNO at DREADDs has never been confirmed.

Identification of Three Novel Radiotracers for Imaging Aggregated Tau in Alzheimer's Disease with Positron Emission Tomography.

Aggregates of tau and beta amyloid (Aβ) plaques constitute the histopathological hallmarks of Alzheimer's disease and are prominent targets for novel therapeutics as well as for biomarkers for diagnostic in vivo imaging. In recent years much attention has been devoted to the discovery and development of new PET tracers to image tau aggregates in the living human brain. Access to a selective PET tracer to image and quantify tau aggregates represents a unique tool to support the development of any novel therapeutic agent targeting pathological forms of tau.

Quantitative Multi-modal Brain Autoradiography of Glutamatergic, Dopaminergic, Cannabinoid, and Nicotinic Receptors in Mutant Disrupted-In-Schizophrenia-1 (DISC1) Mice.

Purpose: Disrupted-in-schizophrenia-1 (DISC1) is a promising genetic susceptibility factor for major psychiatric conditions, such as schizophrenia. We hypothesized that the mutant DISC1 alters the homeostasis of multi-receptor interactions between dopaminergic [dopamine 2/3 (D(2/3)R)], glutamatergic [metabotropic glutamate 5 (mGluR5)], cannabinoid 1 (CB(1)R), and nicotinic acetylcholine (α4β2-nAChR) receptors in the brains of mice with inducible forebrain neuronal expression of dominant-negative mutant DISC1.

Procedures: The quantitative in vitro autoradiography was performed with positron emission tomography (PET) ligands using [(11)C]raclopride (D2/3R), [(11)C]ABP688 (mGluR5), [(11)C]OMAR (CB(1)R), and [(18)F]AZAN (nAChR).

Dose-dependent, saturable occupancy of the metabotropic glutamate subtype 5 receptor by fenobam as measured with [ C]ABP688 PET imaging.

Fenobam is a negative allosteric modulator of the metabotropic glutamate receptor subtype 5 (mGluR5) with inverse agonist activity and is expected to contribute to the treatment of neuropsychiatric disorders involving dysfunction of mGluR5 including Fragile X syndrome. This study examined whether [ C]ABP688, an antagonist PET radioligand, competes with fenobam for the same binding site in the nonhuman primate brain and would allow examination of occupancy-plasma concentration relationships in the evaluation of the drug for target disorders in the human brain. Four paired PET studies with [ C]ABP688 were performed in baboons at a baseline condition and after intravenous treatment with fenobam at different dose levels (0.

Modeling of the renal kinetics of the AT1 receptor specific PET radioligand [11C]KR31173.

Purpose: The radioligand [(11)C]KR31173 has been introduced for PET imaging of the angiotensin II subtype 1 receptor (AT1R). The purpose of the present project was to employ and validate a compartmental model for quantification of the kinetics of this radioligand in a porcine model of renal ischemia followed by reperfusion (IR).

Procedures: Ten domestic pigs were included in the study: five controls and five experimental animals with IR of the left kidney.

Targeting of endothelin receptors in the healthy and infarcted rat heart using the PET tracer 18F-FBzBMS.

Unlabelled: The endothelin subtype-A receptor (ET-A) is a promising therapeutic target in cardiovascular disease. We sought to determine the feasibility of an (18)F-labeled ligand, (18)F-(N-[[29-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl]-4-(2-oxazolyl)[1,19-biphenyl]-2-yl]methyl]-N,4-fluorobenzamide) ((18)F-FBzBMS), for imaging ET-A in the healthy and injured rat heart.

Methods: Male Wistar rats were used for all experiments.

Molecular hybrid positron emission tomography/computed tomography imaging of cardiac angiotensin II type 1 receptors.

Objectives: The goal of this study was to explore the feasibility of targeted imaging of the angiotensin II type 1 receptor (AT1R) in cardiac tissue, using clinical hybrid positron emission tomography/computed tomography (PET/CT).

Background: AT1R is an attractive imaging target due to its key role in various cardiac pathologies, including post-infarct left ventricular remodeling.

Methods: Using the novel AT1R ligand [(11)C]-KR31173, dynamic PET/CT was performed in young farm pigs under healthy conditions (n = 4) and 3 to 4 weeks after experimental myocardial infarction (n = 5).

Molecular imaging of the kidneys.

Radionuclide imaging of the kidneys with gamma cameras involves the use of labeled molecules seeking functionally critical molecular mechanisms to detect the pathophysiology of the diseased kidneys and achieve an early, sensitive, and accurate diagnosis. The most recent imaging technology, positron emission tomography, permits quantitative imaging of the kidney at a spatial resolution appropriate for the organ. H(2)(15)O, (82)RbCl, and [(64)Cu] ETS are the most important radiopharmaceuticals for measuring renal blood flow.