Comparison of high and low molar activity TSPO tracer [F]F-DPA in a mouse model of Alzheimer's disease.

[F]F-DPA, a novel translocator protein 18 kDa (TSPO)-specific radioligand for imaging neuroinflammation, has to date been synthesized with low to moderate molar activities (A's). In certain cases, low A can skew the estimation of specific binding. The high proportion of the non-radioactive component can reduce the apparent-specific binding by competitively binding to receptors.

Effect of genotype and age on cerebral [F]FDG uptake varies between transgenic APP-PS1 and Tg2576 mouse models of Alzheimer's disease.

Back-translation of clinical imaging biomarkers of Alzheimer's disease (AD), such as alterations in cerebral glucose metabolism detected by [F]FDG positron emission tomography (PET), would be valuable for preclinical studies evaluating new disease-modifying drugs for AD. However, previous confounding results have been difficult to interpret due to differences in mouse models and imaging protocols between studies. We used an equivalent study design and [F]FDG µPET imaging protocol to compare changes in cerebral glucose metabolism in commercial transgenic APP-PS1 (n = 12), Tg2576 (n = 15), and wild-type mice (n = 15 and 9).

Radiosynthesis and Preclinical Evaluation of an α-Adrenoceptor Tracer Candidate, 6-[F]Fluoro-marsanidine.

Purpose: The α-adrenoceptors mediate many effects of norepinephrine and epinephrine, and participate in the regulation of neuronal, endocrine, cardiovascular, vegetative, and metabolic functions. Of the three receptor subtypes, only α and α are found in the brain in significant amounts. Subtype-selective positron emission tomography (PET) imaging of α-adrenoceptors has been limited to the α subtype.

characterization of a novel norepinephrine transporter PET tracer [F]NS12137 in adult and immature Sprague-Dawley rats.

Norepinephrine modulates cognitive processes such as working and episodic memory. Pathological changes in norepinephrine and norepinephrine transporter (NET) function and degeneration of the locus coeruleus produce irreversible impairments within the whole norepinephrine system, disrupting cognitive processes. Monitoring these changes could enhance diagnostic accuracy and support development of novel therapeutic components for several neurodegenerative diseases.

[F]F-DPA for the detection of activated microglia in a mouse model of Alzheimer's disease.

Introduction: Neuroinflammation is associated with several neurological disorders, including Alzheimer's disease (AD). The translocator protein 18 kDa (TSPO), due to its overexpression during microglial activation and relatively low levels in the brain under normal neurophysiological conditions, is commonly used as an in vivo biomarker for neuroinflammation. Reported here is the preclinical evaluation of [F]F-DPA, a promising new TSPO-specific radioligand, as a tool for the detection of activated microglia at different ages in the APP/PS1-21 mouse model of AD and a blocking study to determine the specificity of the tracer.

[F]FMPEP-d PET imaging shows age- and genotype-dependent impairments in the availability of cannabinoid receptor 1 in a mouse model of Alzheimer's disease.

Contradictory findings on the role of the type 1 cannabinoid receptor (CBR) during the pathogenesis of Alzheimer's disease (AD) have been reported. Here, we evaluated the CBR brain profile in an AD mouse model using longitudinal positron emission tomography with an inverse agonist for CBR, [F]FMPEP-d. APP/PS1-21 and wild-type (n = 8 in each group) mice were repeatedly imaged between 6 to 15 months of age, accompanied by brain autoradiography, western blot, and CBR immunohistochemistry with additional mice.

F-labeled norepinephrine transporter tracer [F]NS12137: radiosynthesis and preclinical evaluation.

Introduction: Several psychiatric and neurodegenerative diseases are associated with malfunction of brain norepinephrine transporter (NET). However, current clinical evaluations of NET function are limited by the lack of sufficiently sensitive methods of detection. To this end, we have synthesized exo-3-[(6-[F]fluoro-2-pyridyl)oxy]-8-azabicyclo[3.

Radiosynthesis and Preclinical Evaluation of [F]F-DPA, A Novel Pyrazolo[1,5a]pyrimidine Acetamide TSPO Radioligand, in Healthy Sprague Dawley Rats.

Purpose: Many neurological conditions result in the overexpression of the translocator protein 18 kDa (TSPO), today recognized as a biomarker for microglial activation and neuroinflammation imaging. The pyrazolo[1,5-a]pyrimidine acetamides are a particularly attractive class of TSPO-specific ligands, prompting the development of several positron emission tomography (PET) radiotracers. This includes F-DPA, a recently reported fluorinated ligand (K  = 1.

Brain energy metabolism and neuroinflammation in ageing APP/PS1-21 mice using longitudinal F-FDG and F-DPA-714 PET imaging.

Preclinical animal model studies of brain energy metabolism and neuroinflammation in Alzheimer's disease have produced conflicting results, hampering both the elucidation of the underlying disease mechanism and the development of effective Alzheimer's disease therapies. Here, we aimed to quantify the relationship between brain energy metabolism and neuroinflammation in the APP/PS1-21 transgenic mouse model of Alzheimer's disease using longitudinal in vivoF-FDG and F-DPA-714) PET imaging and ex vivo brain autoradiography. APP/PS1-21 (TG, n = 9) and wild type control mice (WT, n = 9) were studied longitudinally every third month from age 6 to 15 months with F-FDG and F-DPA-714 with a one-week interval between the scans.

Monoacylglycerol lipase inhibitor JZL184 reduces neuroinflammatory response in APdE9 mice and in adult mouse glial cells.

Background: Recently, the role of monoacylglycerol lipase (MAGL) as the principal regulator of simultaneous prostaglandin synthesis and endocannabinoid receptor activation in the CNS was demonstrated. To expand upon previously published research in the field, we observed the effect of the MAGL inhibitor JZL184 during the early-stage proinflammatory response and formation of beta-amyloid (Aβ) in the Alzheimer's disease mouse model APdE9. We also investigated its effects in proinflammatory agent - induced astrocytes and microglia isolated from adult mice.