Utilizing Quantitative Analysis of CSF Volume from Clinical T1-Weighted MRI to Predict Thrombectomy Outcomes.

Background And Purpose: Endovascular thrombectomy (EVT) is the standard for acute ischemic stroke from large vessel occlusion, but post-EVT functional independence varies. Brain atrophy, linked to higher cerebrospinal fluid volume (CSFV), may affect outcomes. Baseline CSFV could predict EVT benefit by assessing brain health.

First Biodistribution Study of [68Ga]Ga-NOTA-Insulin Following Intranasal Administration in Adult Vervet Monkeys.

Background: Intranasal insulin (INI) is being explored as a treatment for Alzheimer's disease (AD). Improved memory, functional ability, and cerebrospinal fluid (CSF) AD biomarker profiles have been observed following INI administration. However, the method of intranasal delivery may significantly affect outcomes.

Exploratory Dual PET imaging of [F] fluorodeoxyglucose and [C]acetoacetate in type 2 diabetic nonhuman primates.

Despite recent advancements in imaging (amyloid-PET & tau-PET) and fluid (Aβ42/Aβ40 & Aβ42/ptau) biomarkers, the current standard for in vivo assessment of AD, diagnosis and prediction of Alzheimer's disease (AD) remains challenging. We demonstrated in nonhuman primates (NHP) that increased plasma and cerebrospinal fluid (CSF) glucose correlated with decreased CSF Aβ42 and CSF Aβ40, a hallmark of plaque promoting pathogenesis. Together, our findings demonstrate that altered glucose homeostasis and insulin resistance are associated with Aβ and amyloid in rodent and NHP models.

Exploring microtubule dynamics in Alzheimer's disease: Longitudinal assessment using [C]MPC-6827 PET imaging in rodent models of Alzheimer's-related pathology.

Introduction: Microtubule (MT) stability is crucial for proper neuronal function. Understanding MT dysregulation is critical for connecting amyloid beta (Aβ) and tau-based degenerative events and early changes in presymptomatic Alzheimer's disease (AD). Herein we present positron emission tomography (PET) imaging properties of our MT-PET radiotracer, [C]MPC-6827, in multiple established AD mouse models.

Associations among plasma, MRI, and amyloid PET biomarkers of Alzheimer's disease and related dementias and the impact of health-related comorbidities in a community-dwelling cohort.

Introduction: We evaluated associations between plasma and neuroimaging-derived biomarkers of Alzheimer's disease and related dementias and the impact of health-related comorbidities.

Methods: We examined plasma biomarkers (neurofilament light chain, glial fibrillary acidic protein, amyloid beta [Aβ] 42/40, phosphorylated tau 181) and neuroimaging measures of amyloid deposition (Aβ-positron emission tomography [PET]), total brain volume, white matter hyperintensity volume, diffusion-weighted fractional anisotropy, and neurite orientation dispersion and density imaging free water. Participants were adjudicated as cognitively unimpaired (CU; N = 299), mild cognitive impairment (MCI; N = 192), or dementia (DEM; N = 65).

Two decades of [C]PiB synthesis, 2003-2023: a review.

Because carbon-11 (C) radiotracers cannot be shipped over long distances, their use in routine positron emission tomography (PET) studies is dependent on the production capabilities of individual radiochemistry laboratories. Since 2003, C-labeled Pittsburgh compound B ([C]PiB) has been the gold standard PET radiotracer for imaging of amyloid β (Aβ) plaques. For more than two decades, researchers have been working to develop faster, higher-yielding, more robust, and optimized production methods with higher radiochemical yields for various imaging applications.

Comparison of brain nicotine accumulation from traditional combustible cigarettes and electronic cigarettes with different formulations.

Rapid brain accumulation is critical for the acute reinforcing effects of nicotine. Although nicotine formulation (free-base vs. protonated or salt) in electronic cigarette (E-cig) liquid affects user satisfaction, its impact on brain nicotine accumulation (BNA) from E-cig use has not been evaluated in comparison with traditional combustible cigarettes (C-cigs) using a within-subjects design.

Fully automated production of [C]PiB for clinical use on Trasis-AllinOne synthesizer module.

Pittsburgh compound B ([C]PiB) was the first broadly applied radiotracer with specificity for amyloid-β (Aβ) peptide aggregates in the brain and has since been established as the gold standard for positron emission tomography (PET) employed for clinical in vivo imaging of Aβ plaques, used for imaging applications of Alzheimer's disease (AD), related dementia, and other tauopathies. The use of [C]PiB for routine PET studies is dependent on the production capabilities of each radiochemistry laboratory, subsequently a continuous effort is made to develop suitable and sustainable methods on a variety of auto synthesis platforms. Here we report a fully automated, multi-step radio synthesis, purification, and reformulation of [C]PiB for PET imaging using the Trasis AllinOne synthesis unit, a commonly used commercial radiochemistry module.

Preliminary PET Imaging of Microtubule-Based PET Radioligand [C]MPC-6827 in a Nonhuman Primate Model of Alzheimer's Disease.

The microtubule (MT) instability observed in Alzheimer's disease (AD) is commonly attributed to hyperphosphorylation of the MT-associated protein, tau. PET imaging offers an opportunity to gain critical information about MT changes with the onset and development of AD and related dementia. We developed the first brain-penetrant MT PET ligand, [C]MPC-6827, and evaluated its imaging utility in vervet monkeys.

PET imaging of dopamine transporters and D2/D3 receptors in female monkeys: effects of chronic cocaine self-administration.

Brain imaging studies using positron emission tomography (PET) have shown that long-term cocaine use is associated with lower levels of dopamine (DA) D2/D3 receptors (D2/D3R); less consistent are the effects on DA transporter (DAT) availability. However, most studies have been conducted in male subjects (humans, monkeys, rodents). In this study, we used PET imaging in nine drug-naïve female cynomolgus monkeys to determine if baseline measures of DAT, with [F]FECNT, and D2/D3R availability, with [C]raclopride, in the caudate nucleus, putamen and ventral striatum were associated with rates of cocaine self-administration and if these measures changed during long-term (~13 months) cocaine self-administration and following time-off (3-9 months) from cocaine.

First GPR119 PET Imaging Ligand: Synthesis, Radiochemistry, and Preliminary Evaluations.

G-protein-coupled receptor 119 (GPR119) has emerged as a promising target for treating type 2 diabetes mellitus. Activating GPR119 improves glucose homeostasis, while suppressing appetite and weight gain. Measuring GPR119 levels could significantly advance GPR119-based drug development strategies including target engagement, occupancy, and distribution studies.

Binding Parameters of [C]MPC-6827, a Microtubule-Imaging PET Radiopharmaceutical in Rodents.

Impairment and/or destabilization of neuronal microtubules (MTs) resulting from hyper-phosphorylation of the tau proteins is implicated in many pathologies, including Alzheimer's disease (AD), Parkinson's disease and other neurological disorders. Increasing scientific evidence indicates that MT-stabilizing agents protect against the deleterious effects of neurodegeneration in treating AD. To quantify these protective benefits, we developed the first brain-penetrant PET radiopharmaceutical, [C]MPC-6827, for quantification of MTs in rodent and nonhuman primate models of AD.

Association of dopamine D2-like and D receptor function with initial sensitivity to cocaine reinforcement in male rhesus monkeys.

Identifying neurobiological characteristics that predict the development of cocaine use disorder would be of great value in prevention efforts. Because of their importance in mediating the abuse-related effects of cocaine, brain dopamine receptors are logical candidates for investigation. We analyzed data from two recently published studies that characterized availability of dopamine D2-like receptors (D2R) with [C]raclopride PET imaging and dopamine D receptor (DR) sensitivity with quinpirole-induced yawning in cocaine-naïve rhesus monkeys who subsequently acquired cocaine self-administration and completed a cocaine self-administration dose-effect curve.

Effect of Electronic Cigarette Liquid pH on Retention of 11C-Nicotine in a Respiratory Tract Model.

Introduction: Based on our preliminary 11C-nicotine positron emission tomography (PET) imaging studies in humans, we speculated that greater deposition of nicotine in the respiratory tract from electronic cigarettes compared to combustible cigarettes could result from the alkaline pH of typical aerosol-producing electronic cigarette liquids (e-liquids). To address this hypothesis, we assessed the effect of e-liquid pH on the retention of nicotine in vitro using 11C-nicotine, PET, and a human respiratory tract model of nicotine deposition.

Aims And Methods: A single 2-second 35-mL puff was delivered to a human respiratory tract cast from a 2.

[F]KS1, a novel ascorbate-based ligand images ROS in tumor models of rodents and nonhuman primates.

Over production of reactive oxygen species (ROS) caused by altered redox regulation of signaling pathways is common in many types of cancers. While PET imaging is recognized as the standard tool for cancer imaging, there are no clinically-approved PET radiotracers for ROS-imaging in cancer diagnosis and treatment. An ascorbate-based radio ligand promises to meet this urgent need.

Effects of chronic cocaine and ethanol self-administration on brain dopamine receptors in a rhesus monkey model of polysubstance abuse.

Most individuals with cocaine use disorder also use alcohol; however, little is known about the behavioural and pharmacological mechanisms that promote co-abuse. For example, although studies in humans and animals have documented that chronic use of either alcohol or cocaine alone decreases D2-like receptor (D2R) availability, effects of co-abuse of these substances on dopamine receptor function have not been characterized. These studies examined the effects of long-term cocaine self-administration in 12 male rhesus monkeys who also consumed either ethanol or an ethanol-free solution each day (n = 6 per group).

Comparison of brain nicotine uptake from electronic cigarettes and combustible cigarettes.

Brain accumulation rate and magnitude are critical for the acute reinforcing effects of nicotine. Despite electronic cigarettes' (E-cigs) appeal as substitutes for traditional combustible cigarettes (C-cigs), brain nicotine accumulation (BNA) from E-cigs has not been compared with that from C-cigs using a within-subjects design. BNA was directly assessed with 16 adult dual users (10 females) of E-cigs (e-liquid pH 9.

Preliminary mechanistic insights of a brain-penetrant microtubule imaging PET ligand in a tau-knockout mouse model.

Background: Microtubules (MTs) are critical for cell structure, function, and survival. MT instability may contribute to Alzheimer's disease (AD) pathogenesis as evidenced by persistent negative regulation (phosphorylation) of the neuronal microtubule-associated protein tau. Hyperphosphorylated tau, not bound to MTs, forms intraneuronal pathology that correlates with dementia and can be tracked using positron emission tomography (PET) imaging.

Relapse-like behavior and nAChR sensitization following intermittent access nicotine self-administration.

Many tobacco smokers consume nicotine intermittently, but the underlying mechanisms and neurobiological changes associated with intermittent nicotine intake are unclear. Understanding intermittent nicotine intake is a high priority, as it could promote therapeutic strategies to attenuate tobacco consumption. We examined nicotine intake behavior and neurobiological changes in male rats that were trained to self-administer nicotine during brief (5 min) trials interspersed with longer (15 min) drug-free periods.

Initial Evaluations of the Microtubule-Based PET Radiotracer, [C]MPC-6827 in a Rodent Model of Cocaine Abuse.

Purpose: Microtubules (MTs) are structural units made of α and β tubulin subunits in the cytoskeleton responsible for axonal transport, information processing, and signaling mechanisms-critical for healthy brain function. Chronic cocaine exposure affects the function, organization, and stability of MTs in the brain, thereby impairing overall neurochemical and cognitive processes. At present, we have no reliable, non-invasive methods to image MTs for cocaine use disorder (CUD).

PET Use in Cancer Diagnosis, Treatment, and Prognosis.

Tumorigenesis is a multistep process marked by variations in numerous metabolic pathways that affect cellular architectures and functions. Cancer cells reprogram their energy metabolism to enable several basic molecular functions, including membrane biosynthesis, receptor regulations, bioenergetics, and redox stress. In recent years, cancer diagnosis and treatment strategies have targeted these specific metabolic changes and the tumor's interactions with its microenvironment.

Method to Development of PET Radiopharmaceutical for Cancer Imaging.

The increasing number of different novel positron emission tomography (PET) radiopharmaceuticals poses challenges for their manufacturing procedures at different PET research facilities. Recent commercially available radiochemistry units with disposable cassettes are becoming common stations to produce radiopharmaceuticals with high specifications to understand the critical PET imaging outputs of the study. Therefore, several radiochemists across the PET research centers develop and optimize their own radiochemistry protocols to develop a novel or routine radiopharmaceutical at their lab.

[F]Fluoro-DCP, a first generation PET radiotracer for monitoring protein sulfenylation in vivo.

Redox metabolism plays essential functions in the pathology of cancer and many other diseases. While several radiotracers for imaging redox metabolism have been developed, there are no reports of radiotracers for in vivo imaging of protein oxidation. Here we take the first step towards this goal and describe the synthesis and kinetic properties of a new positron emission tomography (PET) [F]Fluoro-DCP radiotracer for in vivo imaging of protein sulfenylation.