[18F]ZCDD083: a PFKFB3-targeted PET tracer for atherosclerotic plaque imaging

Copyright © 2020 American Chemical Society. Funding We thank the European Union’s Horizon 2020 research and innovation program under the Marie Sklodowska-Curie ITNEuropean Joint Doctorate MOGLYNET (grant agreement No. 675527).Peer reviewedPostprin

Rat Brain Normalization Templates for Robust Regional Analysis of [11C]ABP688 Positron Emission Tomography/Computed Tomography

A methodology to generate rat brain templates for spatial normalization of positron emission tomographic (PET)/computed tomographic (CT) images is described and applied to generate three different templates for imaging of [11C]ABP688, a PET ligand binding to the metabotropic glutamate 5 receptor. The templates are based on functional (PET), structural (CT), and combined PET and CT information, respectively. The templates are created from a test–retest study under normal conditions and are used to assess the different templates by using them in the analysis pipeline of a test–retest and a blocking experiment. The resulting average nondisplaceable binding potentials (BPND) show significant (analysis of variance, p < .05) and substantial (up to 23%) differences between the different approaches in several brain regions. The highest BPND values in receptor-rich regions are obtained using the PET-based approach. This approach also had the smallest variability in all tested regions (standard error of measurement of 9% versus 14% [PET/CT] and 20% [CT]). All approaches showed similar relative changes in BPND values with increased blocking. Taken together, these results suggest that the use of the tracer-specific PET-based template outperforms the other approaches with the performance of the combined PET/CT template between those of the PET and the tracer-independent CT template

Rat brain normalization templates for robust regional analysis of [<tex>^{11}C$</tex>]ABP688 positron emission tomography/computed tomography

A methodology to generate rat brain templates for spatial normalization of positron emission tomographic (PET)/computed tomographic (CT) images is described and applied to generate three different templates for imaging of [ 11 C]ABP688, a PET ligand binding to the metabotropic glutamate 5 receptor. The templates are based on functional (PET), structural (CT), and combined PET and CT information, respectively. The templates are created from a test–retest study under normal conditions and are used to assess the different templates by using them in the analysis pipeline of a test–retest and a blocking experiment. The resulting average nondisplaceable binding potentials (BP ND ) show significant (analysis of variance, p < .05) and substantial (up to 23%) differences between the different approaches in several brain regions. The highest BP ND values in receptor-rich regions are obtained using the PET-based approach. This approach also had the smallest variability in all tested regions (standard error of measurement of 9% versus 14% [PET/CT] and 20% [CT]). All approaches showed similar relative changes in BP ND values with increased blocking. Taken together, these results suggest that the use of the tracer-specific PET-based template outperforms the other approaches with the performance of the combined PET/CT template between those of the PET and the tracer-independent CT template

Radiosynthesis, in vitro and in vivo evaluation of I-123-labeled anandamide analogues for mapping brain FAAH

Fatty acid amide hydrolase (FAAH) is one of the main enzymes responsible for terminating the signaling of endocannabinoids, including anandamide. This paper is the first report of the synthesis, [I-123]-labeling and in vitro and in vivo evaluation of anandamide analogues as potential metabolic trapping radioligands for in vivo evaluation of brain FAAH. N-(2-Iodoethyl)linoleoylamide (2) and N-(2-iodoethyl) arachidonylamide (4) were synthesized with good yields (75% and 86%, respectively) in a two steps procedure starting from their respective acids. In vitro analyses, performed using recombinant rat FAAH and [H-3]-anandamide, demonstrated interaction of 2 and 4 with FAAH (IC50 values of 5.78 lM and 3.14 lM, respectively). [I-123]-2 and [I-123]-4 were synthesized with radiochemical yields of 21% and 12%, respectively, and radiochemical purities were > 90%. Biodistribution studies in mice demonstrated brain uptake for both tracers (maximum values of 1.23% ID/g at 3 min pi for [I-123]-2 and 0.58% ID/g at 10 min pi for [I-123]-4). However, stability studies demonstrated the sensitivity of both tracers to dehalogenation. (c) 2008 Elsevier Ltd. All rights reserved