Non-invasive quantification of stem cell-derived islet graft size and composition.

Aims/hypothesis: Stem cell-derived islets (SC-islets) are being used as cell replacement therapy for insulin-dependent diabetes. Non-invasive long-term monitoring methods for SC-islet grafts, which are needed to detect misguided differentiation in vivo and to optimise their therapeutic effectiveness, are lacking. Positron emission tomography (PET) has been used to monitor transplanted primary islets.

In-target production of [C]CH from a nitrogen/hydrogen gas target as a function of beam current, irradiation time, and target temperature.

Background: Production of [C]CH from gas targets is notorious for weak performance with respect to yield, especially when using high beam currents. Post-target conversion of [C]CO to [C]CH is a widely used roundabout method in C-radiochemistry, but the added complexity increase the challenge to control carrier carbon. Thus in-target-produced [C]CH is superior with respect to molar activity.

Glial reactivity in a mouse model of beta-amyloid deposition assessed by PET imaging of P2X7 receptor and TSPO using [C]SMW139 and [F]F-DPA.

Background: P2X7 receptor has emerged as a potentially superior PET imaging marker to TSPO, the gold standard for imaging glial reactivity. [C]SMW139 is the most recently developed radiotracer to image P2X7 receptor. The aim of this study was to image reactive glia in the APP/PS1-21 transgenic (TG) mouse model of Aβ deposition longitudinally using [C]SMW139 targeting P2X7 receptor and to compare tracer uptake to that of [F]F-DPA targeting TSPO at the final imaging time point.

Evaluation of PET imaging as a tool for detecting neonatal hypoxic-ischemic encephalopathy in a preclinical animal model.

Unlabelled: Hypoxic-ischemic encephalopathy due to insufficient oxygen delivery to brain tissue is a leading cause of death or severe morbidity in neonates. The early recognition of the most severely affected individuals remains a clinical challenge. We hypothesized that hypoxic-ischemic injury can be detected using PET radiotracers for hypoxia ([F]EF5), glucose metabolism ([F]FDG), and inflammation ([F]F-DPA).

Decreased Thalamic Activity Is a Correlate for Disconnectedness during Anesthesia with Propofol, Dexmedetomidine and Sevoflurane But Not S-Ketamine.

Establishing the neural mechanisms responsible for the altered global states of consciousness during anesthesia and dissociating these from other drug-related effects remains a challenge in consciousness research. We investigated differences in brain activity between connectedness and disconnectedness by administering various anesthetics at concentrations designed to render 50% of the subjects unresponsive. One hundred and sixty healthy male subjects were randomized to receive either propofol (1.

[F]Fluoride uptake in various bone types and soft tissues in rat.

Background: In the development of new F-labelled tracers, it is important to assess the amount of released [F]fluoride taken up in the bones of experimental animals because all F-labelled PET-tracers are prone, to lesser or higher degree, to undergo defluorination, with subsequent release of [F]fluoride during scanning. However, the pharmacokinetics of [F]fluoride in bones and other organs of healthy rats have not been well documented in a comprehensive manner. We aimed to study pharmacokinetics of [F]NaF in rats in order to increase our understanding of the biodistribution of [F]fluoride originating from defluorination of F-labelled tracers.

Evaluation of [F]FMTEB in Sprague Dawley rats as a PET tracer for metabotropic glutamate receptor 5.

Introduction: [F]FMTEB, along with other tracers, was developed as a promising PET radioligand for imaging metabotropic glutamate receptor subtype 5 (mGluR5). Despite favorable preliminary results, it has not been used further for studies of mGluR5. This paper presents an in-depth preclinical evaluation of [F]FMTEB in healthy Sprague Dawley rats.

Novel plasma protein binding analysis method for a PET tracer and its radiometabolites: A case study with [C]SMW139 to explain the high uptake of radiometabolites in mouse brain.

Radiometabolites of PET tracers interfere with imaging and need to be taken into account when modeling PET data. Various tracer and radiometabolite characteristics affect the uptake rate into tissue. In this study, we investigated two such factors, lipophilicity and protein-free fraction.

Evaluation of [F]F-DPA PET for Detecting Microglial Activation in the Spinal Cord of a Rat Model of Neuropathic Pain.

Purpose: Recent studies have linked activated spinal glia to neuropathic pain. Here, using a positron emission tomography (PET) scanner with high spatial resolution and sensitivity, we evaluated the feasibility and sensitivity of N,N-diethyl-2-(2-(4-([F]fluoro)phenyl)-5,7-dimethylpyrazolo[1,5-a] pyrimidin-3-yl)acetamide ([F]F-DPA) imaging for detecting spinal cord microglial activation after partial sciatic nerve ligation (PSNL) in rats.

Procedures: Neuropathic pain was induced in rats (n = 20) by PSNL, and pain sensation tests were conducted before surgery and 3 and 7 days post-injury.

Direct Comparison of [F]F-DPA with [F]DPA-714 and [C]PBR28 for Neuroinflammation Imaging in the same Alzheimer's Disease Model Mice and Healthy Controls.

Purpose: In this study we compared the recently developed TSPO tracer [F]F-DPA, with [F]DPA-714 and [C]PBR28 by performing in vivo PET imaging on the same Alzheimer's disease mouse model APP/PS1-21 (TG) and wild-type (WT) mice with all three radiotracers.

Procedures: To compare the radiotracer uptake, percentage of injected dose/mL (%ID/mL), standardized uptake value ratios to cerebellum (SUVR), and voxel-wise analyses were performed.

Results: The peak uptake of [F]F-DPA was higher than 4.

(S)-[F]THK5117 brain uptake is associated with Aβ plaques and MAO-B enzyme in a mouse model of Alzheimer's disease.

The mouse model of beta-amyloid (Aβ) deposition, APP/PS1-21, exhibits high brain uptake of the tau-tracer (S)-[F]THK5117, although no neurofibrillary tangles are present in this mouse model. For this reason we investigated (S)-[F]THK5117 off-target binding to Aβ plaques and MAO-B enzyme in APP/PS1-21 transgenic (TG) mouse model of Aβ deposition. APP/PS1-21 TG and wild-type (WT) control mice in four different age groups (2-26 months) were imaged antemortem by positron emission tomography with (S)-[F]THK5117, and then brain autoradiography.

Intravenous transplantation of olfactory ensheathing cells reduces neuroinflammation after spinal cord injury interleukin-1 receptor antagonist.

Olfactory ensheathing cell (OEC) transplantation has emerged as a promising therapy for spinal cord injury (SCI) repair. In the present study, we explored the possible mechanisms of OECs transplantation underlying neuroinflammation modulation. Spinal cord inflammation after intravenous OEC transplantation was detected and by translocator protein PET tracer [F]F-DPA.

Application of the PET ligand [C]ORM-13070 to examine receptor occupancy by the α-adrenoceptor antagonist ORM-12741: translational validation of target engagement in rat and human brain.

Background: Availability of the α-adrenoceptor (α-AR) positron emission tomography (PET) tracer, [C]ORM-13070, and the α-AR antagonist ORM-12741 allows probing of the roles of this G-protein coupled receptor subtype in brain function, both in healthy humans and in patients with various brain disorders. This translational study employed [C]ORM-13070 autoradiography and PET to determine α-AR occupancy by ORM-12741 in rat and human brain, respectively.

Results: ORM-12741 has high affinity (K: 0.

Ruthenium-Mediated F-Fluorination and Preclinical Evaluation of a New CB Receptor Imaging Agent [F]FPATPP.

Cannabinoid receptor 1 (CB1R) controls various physiological and pathological conditions, including memory, motivation, and inflammation, and is thus an interesting target for positron emission tomography (PET). Herein, we report a ruthenium-mediated radiolabeling synthesis and preclinical evaluation of a new CB1R specific radiotracer, [F]FPATPP. [F]FPATPP was produced with 16.

Automated GMP production and long-term experience in radiosynthesis of CB tracer [ F]FMPEP-d.

Here, we describe the development of an in-house-built device for the fully automated multistep synthesis of the cannabinoid CB receptor imaging tracer (3R,5R)-5-(3-([ F]fluoromethoxy-d )phenyl)-3-(((R)-1-phenylethyl)amino)-1-(4-(trifluoromethyl)phenyl)pyrrolidin-2-one ([ F]FMPEP-d ), following good manufacturing practices. The device is interfaced to a HPLC and a sterile filtration unit in a clean room hot cell. The synthesis involves the nucleophilic F-fluorination of an alkylating agent and its GC purification, the subsequent F-fluoroalkylation of a precursor molecule, the semipreparative HPLC purification of the F-fluoroalkylated product, and its formulation for injection.

[F]SPA-RQ/PET Study of NK1 receptors in the Whole Body of Guinea Pig and Rat.

There is a substantial interest in the development of NK1 substance P antagonists as potential treatments for various neuropsychiatric and somatic disorders. The aim of this study was to determine whether [F]SPA-RQ can be utilized as a tool for studying the whole body distribution and function of NK1 receptors in preclinical settings. The compound was injected into guinea pigs with or without premedication with a NK1 receptor antagonist (NK1A-2).

In Vivo Availability of Cannabinoid 1 Receptor Levels in Patients With First-Episode Psychosis.

Importance: Experimental and epidemiological studies implicate the cannabinoid 1 receptor (CB1R) in the pathophysiology of psychosis. However, whether CB1R levels are altered in the early stages of psychosis and whether they are linked to cognitive function or symptom severity remain unknown.

Objective: To investigate CB1R availability in first-episode psychosis (FEP) without the confounds of illness chronicity or the use of illicit substances or antipsychotics.

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.

Effects of short-term sprint interval and moderate-intensity continuous training on liver fat content, lipoprotein profile, and substrate uptake: a randomized trial.

Type 2 diabetes (T2D) and increased liver fat content (LFC) alter lipoprotein profile and composition and impair liver substrate uptake. Exercise training mitigates T2D and reduces LFC, but the benefits of different training intensities in terms of lipoprotein classes and liver substrate uptake are unclear. The aim of this study was to evaluate the effects of moderate-intensity continuous training (MICT) or sprint interval training (SIT) on LFC, liver substrate uptake, and lipoprotein profile in subjects with normoglycemia or prediabetes/T2D.

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.

Identification of new molecular targets for PET imaging of the microglial anti-inflammatory activation state.

Microglia are potential targets for therapeutic intervention in neurological and neurodegenerative diseases affecting the central nervous system. In order to assess the efficacy of therapies aimed to reduce the tissue damaging activities of microglia and/or to promote the protective potential of these cells, suitable pre-clinical and clinical tools for the analysis of microglia activities and dynamics are required. The aim of this work was to identify new translational markers of the anti-inflammatory / protective state of microglia for the development of novel PET tracers.