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Purpose: We report findings from the first-in-human study of [ 11 C]MDTC, a radiotracer developed to image the cannabinoid receptor type 2 (CB2R) with positron emission tomography (PET). Methods: Ten healthy adults were imaged according to a 90 min dynamic PET protocol after bolus intravenous injection of [ 11 C]MDTC. Five participants also completed a second [ 11 C]MDTC PET scan to assess test-retest reproducibility of receptor-binding outcomes. The kinetic behavior of [ 11 C]MDTC in human brain was evaluated using a metabolite-corrected arterial plasma input function with compartmental modeling and graphical analysis approaches. Four additional healthy adults completed whole-body [ 11 C]MDTC PET/CT to calculate organ doses and the whole-body effective dose. Results: [ 11 C]MDTC brain PET and [ 11 C]MDTC whole body PET/CT was well-tolerated. The model of choice for fitting the time activity curves (TACs) across brain regions of interest was a two-tissue compartment model with the blood volume fraction included as a fitting parameter (2TCM-vB). Regional distribution volume (V T ) values computed from Logan graphical analysis correlated well with those estimated using the 2TCM-vB model. Cortical regions and thalamus had higher V T than brainstem, striatum, hippocampus, and corpus callosum. Test-retest reliability of V T demonstrated a mean absolute variability of 7.13%, with an intraclass correlation coefficient 0.91. The measured effective dose of [ 11 C]MDTC was 5.29 µSv/MBq. Conclusion: These data support use of [ 11 C]MDTC PET for in vivo neuroimaging of CB2R in humans. Future in vivo studies using [ 11 C]MDTC PET in neuroinflammatory conditions are needed to assess the detection of high expression of the CB2R by activated microglia in human brain.

Emerging evidence supports a hypothesized role for the α7-nicotinic acetylcholine receptor (α7-nAChR) in the pathophysiology of Alzheimer's disease. 18F-ASEM (3-(1,4-diazabicyclo[3.2.2]nonan-4-yl)-6-18F-fluorodibenzo[b,d]thiophene 5,5-dioxide) is a radioligand for estimating the availability of α7-nAChR in the brain in vivo with PET. Methods: In this cross-sectional study, 14 patients with mild cognitive impairment (MCI), a prodromal stage to dementia, and 17 cognitively intact, elderly controls completed 18F-ASEM PET. For each participant, binding in each region of interest was estimated using Logan graphical analysis with a metabolite-corrected arterial input function. Results: Higher 18F-ASEM binding was observed in MCI patients than in controls across all regions, supporting higher availability of α7-nAChR in MCI. 18F-ASEM binding was not associated with verbal memory in this small MCI sample. Conclusion: These data support use of 18F-ASEM PET to examine further the relationship between α7-nAChR availability and MCI.

Soluble epoxide hydrolase (sEH) is an enzyme with putative effect on neuroinflammation through its influence on the homeostasis of polyunsaturated fatty acids and related biproducts. Since sEH is an enzyme that metabolizes the anti-inflammatory epoxy fatty acids to relatively inert 1,2-diol forms, a high availability or activity of sEH may promote vasoconstriction and inflammation in local tissues that may be linked to neuropsychiatric disease such as depressive disorders. [(18)F]FNDP is a radiotracer developed by our group for studying sEH in the living human brain with positron emission tomography (PET). METHODS: Brain PET using bolus injection of [(18)F]FNDP followed by emission imaging lasting 90 or 180 min was completed in seven healthy adults (5 males, 2 females, ages 40–53 years). The kinetic behavior of [(18)F]FNDP was evaluated using a metabolite corrected arterial plasma input function with compartmental or graphical modeling approaches. RESULTS: [(18)F]FNDP PET was well tolerated. Akaike information criterion favored the two-tissue compartment model (2TCM) in all ten regions of interest. Regional total distribution volume (V(T)) values from each compartmental model and Logan analysis were generally well-identified except corpus callosum V(T) using 2TCM. Logan analysis was assessed as the choice model due to stability of the regional V(T) values from 90 min data and due to high correlation of Logan-derived regional V(T) values with those from the 2TCM. The distribution of sEH differed from that of our prior study of primate brain, with higher binding in human cerebellar cortex and thalamus relative to other cortical regions, which aligns with reported consensus expression patterns of the epoxide hydrolase 2 gene in human brain. CONCLUSION: These data support further use of [(18)F]FNDP PET to study sEH in human brain.

Emerging evidence supports a hypothesized role for the α7-nicotinic acetylcholine receptor (α7-nAChR) in the pathophysiology of Alzheimer’s disease. (18)F-ASEM (3-(1,4-diazabicyclo[3.2.2]nonan-4-yl)-6-(18)F-fluorodibenzo[b,d]thiophene 5,5-dioxide) is a radioligand for estimating the availability of α7-nAChR in the brain in vivo with PET. Methods: In this cross-sectional study, 14 patients with mild cognitive impairment (MCI), a prodromal stage to dementia, and 17 cognitively intact, elderly controls completed (18)F-ASEM PET. For each participant, binding in each region of interest was estimated using Logan graphical analysis with a metabolite-corrected arterial input function. Results: Higher (18)F-ASEM binding was observed in MCI patients than in controls across all regions, supporting higher availability of α7-nAChR in MCI. (18)F-ASEM binding was not associated with verbal memory in this small MCI sample. Conclusion: These data support use of (18)F-ASEM PET to examine further the relationship between α7-nAChR availability and MCI.