Selective Mu-Opioid Receptor Imaging Using F-Labeled Carfentanils.

Carfentanil, a highly potent synthetic opioid, paradoxically serves as a crucial positron emission tomography (PET) imaging tool in neurobiological studies of the mu-opioid receptor (MOR) system when labeled with carbon-11 ([C]CFN). However, its clinical research use is hindered by extreme potency and the limited availability of short-lived carbon-11 ( = 20.4 min).

Deciphering the effects of radiopharmaceutical therapy in the tumor microenvironment of prostate cancer: an in-silico exploration with spatial transcriptomics.

Radiopharmaceutical therapy (RPT) is an emerging prostate cancer treatment that delivers radiation to specific molecules within the tumor microenvironment (TME), causing DNA damage and cell death. Given TME heterogeneity, it's crucial to explore RPT dosimetry and biological impacts at the cellular level. We integrated spatial transcriptomics (ST) with computational modeling to investigate the effects of RPT targeting prostate-specific membrane antigen (PSMA), fibroblast activation protein (FAP), and gastrin-releasing peptide receptor (GRPR) each labelled with beta-emitting lutetium-177 (Lu) and alpha-emitting actinium-225 (Ac).

PET mapping of receptor occupancy using joint direct parametric reconstruction.

Unlabelled: Receptor occupancy (RO) studies using PET neuroimaging play a critical role in the development of drugs targeting the central nervous system (CNS). The conventional approach to estimate drug receptor occupancy consists in estimation of binding potential changes between two PET scans (baseline and post-drug injection). This estimation is typically performed separately for each scan by first reconstructing dynamic PET scan data before fitting a kinetic model to time activity curves.

Free-breathing 3D cardiac extracellular volume (ECV) mapping using a linear tangent space alignment (LTSA) model.

Purpose: To develop a new method for free-breathing 3D extracellular volume (ECV) mapping of the whole heart at 3 T.

Methods: A free-breathing 3D cardiac ECV mapping method was developed at 3 T. T mapping was performed before and after contrast agent injection using a free-breathing electrocardiogram-gated inversion recovery sequence with spoiled gradient echo readout.

Free-breathing 3D cardiac extracellular volume (ECV) mapping using a linear tangent space alignment (LTSA) model.

$\textbf{Purpose:}$ To develop a new method for free-breathing 3D extracellular volume (ECV) mapping of the whole heart at 3T. $\textbf{Methods:}$ A free-breathing 3D cardiac ECV mapping method was developed at 3T. T1 mapping was performed before and after contrast agent injection using a free-breathing ECG-gated inversion-recovery sequence with spoiled gradient echo readout.

Distinct neural mechanisms for heading retrieval and context recognition in the hippocampus during spatial reorientation.

Reorientation, the process of regaining one's bearings after becoming lost, requires identification of a spatial context (context recognition) and recovery of facing direction within that context (heading retrieval). We previously showed that these processes rely on the use of features and geometry, respectively. Here, we examine reorientation behavior in a task that creates contextual ambiguity over a long timescale to demonstrate that male mice learn to combine both featural and geometric cues to recover heading.

Radiosynthesis automation, non-human primate biodistribution and dosimetry of K channel tracer [C]3MeO4AP.

Background: 4-Aminopyridine (4AP) is a medication for the symptomatic treatment of multiple sclerosis. Several 4AP-based PET tracers have been developed for imaging demyelination. In preclinical studies, [C]3MeO4AP has shown promise due to its high brain permeability, high metabolic stability, high plasma availability, and high in vivo binding affinity.

PET imaging of M4 muscarinic acetylcholine receptors in rhesus macaques using [C]MK-6884: Quantification with kinetic modeling and receptor occupancy by CVL-231 (emraclidine), a novel positive allosteric modulator.

Stimulation of the M muscarinic acetylcholine receptor reduces striatal hyperdopaminergia, suggesting its potential as a therapeutic target for schizophrenia. Emraclidine (CVL-231) is a novel, highly selective, positive allosteric modulator (PAM) of M4 muscarinic acetylcholine receptors i.e.

Acute Stress Increases Striatal Connectivity With Cortical Regions Enriched for μ and κ Opioid Receptors.

Background: Understanding the neurobiological effects of stress is critical for addressing the etiology of major depressive disorder (MDD). Using a dimensional approach involving individuals with differing degree of MDD risk, we investigated 1) the effects of acute stress on cortico-cortical and subcortical-cortical functional connectivity (FC) and 2) how such effects are related to gene expression and receptor maps.

Methods: Across 115 participants (37 control, 39 remitted MDD, 39 current MDD), we evaluated the effects of stress on FC during the Montreal Imaging Stress Task.

Head-to-head comparison of [F]-Flortaucipir, [F]-MK-6240 and [F]-PI-2620 postmortem binding across the spectrum of neurodegenerative diseases.

We and others have shown that [F]-Flortaucipir, the most validated tau PET tracer thus far, binds with strong affinity to tau aggregates in Alzheimer's (AD) but has relatively low affinity for tau aggregates in non-AD tauopathies and exhibits off-target binding to neuromelanin- and melanin-containing cells, and to hemorrhages. Several second-generation tau tracers have been subsequently developed. [F]-MK-6240 and [F]-PI-2620 are the two that have garnered most attention.

Evaluation of - and -4-[F]fluorogabapentin for brain PET imaging.

Gabapentin, a selective ligand for the α2δ subunit of voltage-dependent calcium channels, is an anticonvulsant medication used in the treatment of neuropathic pain, epilepsy and other neurological conditions. We recently described two radiofluorinated derivatives of gabapentin (4-[F]fluorogabapentin, [F]tGBP4F, and 4-[F]fluorogabapentin, [F]cGBP4F) and showed that these compounds accumulate in the injured nerves in a rodent model of neuropathic pain. Given the use of gabapentin in brain diseases, here we investigate whether these radiofluorinated derivatives of gabapentin can be used for imaging α2δ receptors in the brain.

Association of Novelty-Related Locus Coeruleus Function With Entorhinal Tau Deposition and Memory Decline in Preclinical Alzheimer Disease.

Background And Objectives: The predictable Braak staging scheme suggests that cortical tau progression may be related to synaptically connected neurons. Animal and human neuroimaging studies demonstrated that changes in neuronal activity contribute to tau spreading. Whether similar mechanisms explain tau progression from the locus coeruleus (LC), a tiny noradrenergic brainstem nucleus involved in novelty, learning, and memory and among the earliest regions to accumulate tau, has not yet been established.

Tau Positron Emission Tomography and Neurocognitive Function Among Former Professional American-Style Football Players.

American-style football (ASF) players experience repetitive head impacts that may result in chronic traumatic encephalopathy neuropathological change (CTE-NC). At present, a definitive diagnosis of CTE-NC requires the identification of localized hyperphosphorylated Tau (p-Tau) after death via immunohistochemistry. Some studies suggest that positron emission tomography (PET) with the radiotracer [F]-Flortaucipir (FTP) may be capable of detecting p-Tau and thus establishing a diagnosis of CTE-NC among living former ASF players.

Impact of motion correction on [F]-MK6240 tau PET imaging.

. Positron emission tomography (PET) imaging of tau deposition using [F]-MK6240 often involves long acquisitions in older subjects, many of whom exhibit dementia symptoms. The resulting unavoidable head motion can greatly degrade image quality.

Radiosynthesis automation, non-human primate biodistribution and dosimetry of K channel tracer [ C]3MeO4AP.

Purpose: 4-Aminopyridine (4AP) is a medication for the symptomatic treatment of multiple sclerosis. Several 4AP-based PET tracers have been developed for imaging demyelination. In preclinical studies, [ C]3MeO4AP has shown promise due to its high brain permeability, high metabolic stability, high plasma availability, and high binding affinity.

Distinct neural mechanisms for heading retrieval and context recognition in the hippocampus during spatial reorientation.

Reorientation, the process of regaining one's bearings after becoming lost, requires identification of a spatial context (context recognition) and recovery of heading direction within that context (heading retrieval). We previously showed that these processes rely on the use of features and geometry, respectively. Here, we examine reorientation behavior in a task that creates contextual ambiguity over a long timescale to demonstrate that mice learn to combine both featural and geometric cues to recover heading with experience.

Measurement of Cerebral Perfusion Indices from the Early Phase of [F]MK6240 Dynamic Tau PET Imaging.

6-(fluoro-F)-3-(1H-pyrrolo[2,3-c]pyridin-1-yl)isoquinolin-5-amine ([F]MK6240) has high affinity and selectivity for hyperphosphorylated tau and readily crosses the blood-brain barrier. This study investigated whether the early phase of [F]MK6240 can be used to provide a surrogate index of cerebral perfusion. Forty-nine subjects who were cognitively normal (CN), had mild cognitive impairment (MCI), or had Alzheimer's disease (AD) underwent paired dynamic [F]MK6240 and [C]Pittsburgh compound B (PiB) PET, as well as structural MRI to obtain anatomic information.

Super-resolution in brain positron emission tomography using a real-time motion capture system.

Super-resolution (SR) is a methodology that seeks to improve image resolution by exploiting the increased spatial sampling information obtained from multiple acquisitions of the same target with accurately known sub-resolution shifts. This work aims to develop and evaluate an SR estimation framework for brain positron emission tomography (PET), taking advantage of a high-resolution infra-red tracking camera to measure shifts precisely and continuously. Moving phantoms and non-human primate (NHP) experiments were performed on a GE Discovery MI PET/CT scanner (GE Healthcare) using an NDI Polaris Vega (Northern Digital Inc), an external optical motion tracking device.

Kinetic evaluation and assessment of longitudinal changes in reference region and extracerebral [F]MK-6240 PET uptake.

[F]MK-6240 meningeal/extracerebral off-target binding may impact tau quantification. We examined the kinetics and longitudinal changes of extracerebral and reference regions. [F]MK-6240 PET was performed in 24 cognitively-normal and eight cognitively-impaired subjects, with arterial samples in 13 subjects.

Radiochemical Synthesis and Evaluation of 3-[C]Methyl-4-aminopyridine in Rodents and Nonhuman Primates for Imaging Potassium Channels in the CNS.

Demyelination, the loss of the insulating sheath of neurons, causes failed or slowed neuronal conduction and contributes to the neurological symptoms in multiple sclerosis, traumatic brain and spinal cord injuries, stroke, and dementia. In demyelinated neurons, the axonal potassium channels K1.1 and K1.