Abstract
Purpose
The aim of this study was to evaluate different non-invasive methods for generating (R)-1-((3-([11C]methyl)pyridin-4-yl)methyl)-4-(3,4,5-trifluorophenyl)pyrrolidin-2-one) ([11C]UCB-J) parametric maps using white matter (centrum semi-ovale–SO) as reference tissue.
Procedures
Ten healthy volunteers (8 M/2F; age 27.6 ± 10.0 years) underwent a 90-min dynamic [11C]UCB-J positron emission tomography (PET) scan with full arterial blood sampling and metabolite analysis before and after administration of a novel chemical entity with high affinity for presynaptic synaptic vesicle glycoprotein 2A (SV2A). A simplified reference tissue model (SRTM2), multilinear reference tissue model (MRTM2), and reference Logan graphical analysis (rLGA) were used to generate binding potential maps using SO as reference tissue (BPSO). Shorter dynamic acquisitions down to 50 min were also considered. In addition, standard uptake value ratios (SUVR) relative to SO were evaluated for three post-injection intervals (SUVRSO,40-70min, SUVRSO,50-80min, and SUVRSO,60-90min respectively). Regional parametric BPSO + 1 and SUVRSO were compared with regional distribution volume ratios of a 1-tissue compartment model (1TCM DVRSO) using Spearman correlation and Bland-Altman analysis.
Results
For all methods, highly significant correlations were found between regional, parametric BPSO + 1 (r = [0.63;0.96]) or SUVRSO (r = [0.90;0.91]) estimates and regional 1TCM DVRSO. For a 90-min dynamic scan, parametric SRTM2 and MRTM2 values presented similar small bias and variability (− 3.0 ± 2.9 % for baseline SRTM2) and outperformed rLGA (− 10.0 ± 5.3 % for baseline rLGA). Reducing the dynamic acquisition to 60 min had limited impact on the bias and variability of parametric SRTM2 BPSO estimates (− 1.0 ± 9.9 % for baseline SRTM2) while a higher variability (− 1.83 ± 10.8 %) for baseline MRTM2 was observed for shorter acquisition times. Both SUVRSO,60-90min and SUVRSO,50-80min showed similar small bias and variability (− 2.8 ± 4.6 % bias for baseline SUVRSO,60-90min).
Conclusion
SRTM2 is the preferred method for a voxelwise analysis of dynamic [11C]UCB-J PET using SO as reference tissue, while reducing the dynamic acquisition to 60 min has limited impact on [11C]UCB-J BPSO parametric maps. For a static PET protocol, both SUVRSO,60-90min and SUVRSO,50-80min images are an excellent proxy for [11C]UCB-J BPSO parametric maps.
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Acknowledgments
The authors thank the participants in addition to the investigators and their teams who contributed to this study. We also thank Kwinten Porters and Jef Van Loock (department Nuclear Medicine, UZ Leuven) for their technical assistance, and the UZ Leuven radiopharmacy team for the tracer productions. We also acknowledge Barbara Pelgrims, PhD, (UCB Pharma, Brussels, BE) for publication coordination.
Funding
Part of this study was sponsored by a UCB Pharma research grant of UCB-J to KU Leuven (principal investigator Koen Van Laere).
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Ralph Paul Maguire, Brigitte Lacroix, Joel Mercier, and David Sciberras are employees of UCB Pharma. Nathalie Mertens, Kim Serdons, Koen Van Laere, and Michel Koole have no conflicts of interest to disclose.
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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. All subjects signed informed consent before entering the study.
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Mertens, N., Maguire, R.P., Serdons, K. et al. Validation of Parametric Methods for [11C]UCB-J PET Imaging Using Subcortical White Matter as Reference Tissue. Mol Imaging Biol 22, 444–452 (2020). https://doi.org/10.1007/s11307-019-01387-6
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DOI: https://doi.org/10.1007/s11307-019-01387-6