Comparison of standardized uptake values with volume of distribution for quantitation of [11C]PBR28 brain uptake

Abstract

Introduction: [11C]PBR28 is a high-affinity ligand for the Translocator Protein 18kDa (TSPO), which is considered to be a marker for microglial activation. Volume of distribution (VT) estimated with an arterial plasma input function is the gold standard for quantitation of [11C]PBR28 binding. However, arterial sampling is impractical at many PET sites for multiple reasons. Reference region modeling approaches are not ideal for TSPO tracers, as the existence of a true reference region cannot be assumed. Given that it would be desirable to have a non-invasive index of [11C]PBR28 binding, we elected to study the utility of the semi-quantitative metric, standardized uptake value (SUV) for use in brain [11C]PBR PET studies. The primary goal of this study was to determine the relationship between SUV and VT. Methods: We performed a retrospective analysis of data from sixteen [11C]PBR28 PET scans acquired in baboons at baseline and at multiple time points after IV injection of lipopolysaccharide, an endotoxin that transiently induces neuroinflammation. For each scan, data from 14 brain regions of interest were studied. VT was estimated with the Logan plot, using metabolite-corrected input functions. SUV was calculated with data from 30 to 60minutes after [11C]PBR28 injection. Results: Within individual PET studies, SUV tended to correlate well with VT. Across studies, the relationship between SUV and VT was variable. Conclusions: From study to study, there was variability in the degree of correlation between [11C]PBR28 VT and SUV. There are multiple physiological factors that may contribute to this variance. Advances in Knowledge: As currently applied, the non-invasive measurement of SUV does not appear to be a reliable outcome variable for [11C]PBR28. Additional work is needed to discover the source of the discrepancy in SUV between [11C]PBR28 scans. Implications for Patient Care: There is a need to develop alternatives to arterial plasma input functions for TSPO ligands in order to facilitate multi-center trials.