This study aimed to investigate morphological and metabolic changes in the brains of 5xFAD mice. Structural magnetic resonance imaging (MRI) and ¹H magnetic resonance spectroscopy (MRS) were obtained in 10- and 14-month-old 5xFAD and wild-type (WT) mice, while ³¹P MRS scans were acquired in 11-month-old mice. Significantly reduced gray matter (GM) was identified by voxel-based morphometry (VBM) in the thalamus, hypothalamus, and periaqueductal gray areas of 5xFAD mice compared to WT mice. Significant reductions in N-acetyl aspartate and elevation of myo-Inositol were revealed by the quantification of MRS in the hippocampus of 5xFAD mice, compared to WT. A significant reduction in NeuN-positive cells and elevation of Iba1- and GFAP-positive cells supported this observation. The reduction in phosphomonoester and elevation of phosphodiester was observed in 11-month-old 5xFAD mice, which might imply a sign of disruption in the membrane synthesis. Commonly reported ¹H MRS features were replicated in the hippocampus of 14-month-old 5xFAD mice, and a sign of disruption in the membrane synthesis and elevation of breakdown were revealed in the whole brain of 5xFAD mice by ³¹P MRS. GM volume reduction was identified in the thalamus, hypothalamus, and periaqueductal gray areas of 5xFAD mice.

Background/Objectives: Quantitative PET imaging of μ-opioid receptor (MOR) availability and pharmacologic engagement can advance in vivo studies of opioid receptor biology. We previously evaluated a series of ¹⁸F-labeled carfentanil analogs and prioritized the regioisomer [¹⁸F]fluorocarfentanil ([¹⁸F]FCFN) based on favorable brain kinetics, regional distribution, and naloxone-sensitive binding. Here, we provide proof-of-concept evaluation of [¹⁸F]FCFN in rhesus macaques to assess its potential for quantitative, pharmacologically responsive MOR PET. Methods: [¹⁸F]FCFN was produced by automated radiosynthesis. Dynamic [¹⁸F]FCFN PET scans were performed in two rhesus macaques under baseline conditions, after low- (0.005 mg/kg) and high-dose (0.2 mg/kg) naloxone pretreatment, and during within-scan intravenous or intranasal naloxone challenge. For arterial input scans, two-tissue compartment modeling with metabolite-corrected arterial input functions was used to estimate total distribution volume (V_T). Nondisplaceable binding potential (BP_ND) was estimated using multilinear reference tissue model 2 with the cerebellum as the candidate reference region. Results: Automated radiosynthesis produced [¹⁸F]FCFN in high radiochemical yield and molar activity, enabling low-mass PET injections (0.09–0.32 μg). [¹⁸F]FCFN showed rapid brain uptake and MOR-consistent regional distribution, with lowest uptake in the cerebellum. Regional BP_ND correlated positively with V_T at baseline (R² = 0.983, p < 0.0001) and after high-dose blockade (R² = 0.522, p < 0.004). Naloxone pretreatment reduced regional BP_ND in a dose-dependent manner. Within-scan intravenous and intranasal naloxone challenges also produced marked reductions in BP_ND. Conclusions: [¹⁸F]FCFN enables quantitative, pharmacologically sensitive MOR PET imaging in nonhuman primates at low injected masses. Concordant plasma-input and reference-tissue measures, dose-dependent blockade, and proof-of-concept within-scan displacement support its use for measuring MOR availability and dynamic antagonist engagement across administration routes.

The goal of this study was to generate a population-based template/atlas and apply the template/atlas-based attenuation correction (AC) method for simultaneous positron-emission-tomography/magnetic-resonance-imaging (PET/MRI) neuroimaging studies on non-human primates (NHPs). Population-based template/atlas of computed tomography image and anatomical MRI, were generated from ten NHPs (rhesus macaque). By using the generated template/atlas, the linear attenuation coefficient (LAC) of objects can be reliably derived, showing good differentiation for tissues, also skull and air. Comparison of the PET images reconstructed by the template/atlas-based and simple threshold-based AC has shown that the template/atlas-based AC can increase PET signal by avoiding overcompensation of attenuation.

The cannabinoid 1 receptor (CB1R) is a key pharmacological target in the central nervous system, modulating emotions, cognition, and memory. Functional interactions between CB1R and mu-opioid receptors (MOR) in analgesia have been reported. This study investigated CB1R occupancy and neuronal activation in non-human primate brains following acute administration of a CB1R agonist (CP55,940), an antagonist/inverse-agonist (rimonabant), an MOR agonist (morphine) using simultaneous positron emission tomography (PET) and functional magnetic resonance imaging (fMRI). [ ¹¹ C]OMAR, a CB1R-selective radiotracer, PET scans were acquired using bolus or bolus-plus-infusion protocols. Rimonabant (1, 3 mg/kg, n = 1 for each) reduced [ ¹¹ C]OMAR non-displaceable binding potential by 25%–40% in CB1R-rich regions. To our knowledge, this is the first in vivo demonstration of CB1R occupancy by the agonist CP55,940 (0.05 mg/kg, n = 2), which displaced 15%–30% of [ ¹¹ C]OMAR volume of distribution (V _T ) in CB1R-rich regions. Although there was no clear dose–response relationship, CP55,940 increased cerebral blood volume (CBV), whereas rimonabant caused a biphasic response. Morphine administration (1 mg/kg, n = 2) reduced CBV in MOR-rich areas and modestly increased [ ¹¹ C]OMAR V _T , suggesting a potential indirect modulation of CB1R availability. Given the small sample size and variability close to test–retest levels, these preliminary findings should be interpreted with caution.