Reliable quantification of 18F-GE-180 PET neuroinflammation studies using an individually scaled population-based input function or late tissue-to-blood ratio

Abstract

Purpose Tracer kinetic modeling of tissue time activity curves and the individual input function based on arterial blood sampling and metabolite correction is the gold standard for quantitative characterization of microglia activation by PET with the translocator protein (TSPO) ligand 18 F-GE-180. This study tested simplified methods for quantification of 18 F-GE-180 PET. Methods Dynamic 18 F-GE-180 PET with arterial blood sampling and metabolite correction was performed in five healthy volunteers and 20 liver-transplanted patients. Population-based input function templates were generated by averaging individual input functions normalized to the total area under the input function using a leave-one-out approach. Individual population-based input functions were obtained by scaling the input function template with the individual parent activity concentration of 18 F-GE-180 in arterial plasma in a blood sample drawn at 27.5 min or by the individual administered tracer activity, respectively. The total 18 F-GE-180 distribution volume (V T) was estimated in 12 regions-of-interest (ROIs) by the invasive Logan plot using the measured or the population-based input functions. Late ROI-to-whole-blood and ROI-to-cerebellum ratio were also computed. Results Correlation with the reference V T (with individually measured input function) was very high for V T with the populationbased input function scaled with the blood sample and for the ROI-to-whole-blood ratio (Pearson correlation coefficient = 0.989 ± 0.006 and 0.970 ± 0.005). The correlation was only moderate for V T with the population-based input function scaled with tracer activity dose and for the ROI-to-cerebellum ratio (0.653 ± 0.074 and 0.384 ± 0.177). Reference V T , population-based V T with scaling by the blood sample, and ROI-to-whole-blood ratio were sensitive to the TSPO gene polymorphism. Population-based V T with scaling to the administered tracer activity and the ROI-to-cerebellum ratio failed to detect a polymorphism effect. Conclusion These results support the use of a population-based input function scaled with a single blood sample or the ROI-towhole-blood ratio at a late time point for simplified quantitative analysis of 18 F-GE-180 PET.

Population-based input function for TSPO quantification and kinetic modeling with [11C]-DPA-713

“…3 and Supplementary Figure S2 ) however showed no significant difference in PSAIF between the groups, and so, all subject PSAIFs were included in the generation of the PBIF. This was also in agreement with other studies [ 27 , 51 ].…”

“…Precisely, the AUC between PSAIF and PBIF was minimized by scaling the PBIF with an arterial blood value at 75 min, as also recommended by past similar TSPO studies [ 27 , 51 ]. It has been shown that venous blood samples may practically be used instead for scaling purpose since arterial and venous blood tend to reach equilibrium at about 30–45 min post-injection time [ 17 ].…”

“…It has been shown that venous blood samples may practically be used instead for scaling purpose since arterial and venous blood tend to reach equilibrium at about 30–45 min post-injection time [ 17 ]. Although this was not tested in this work, but similar TSPO studies have also found that PBIF can be appropriately scaled using one blood sample [ 27 , 51 ]. Since the utmost aim is to potentially alleviate the need for arterial blood sampling, the AUC component of the PBIF normalization can be obtained by scaling the normalized PBIF by the ratio of the average activity concentration of blood samples (possibly venous blood) acquired over the last 30 min of the dynamic scan (i.e., between 60 and 90 min) and that of the tail of the PBIF over the same time frames (as was done in this study).…”

Population-Based Input Function for TSPO Quantification and Kinetic Modeling with [11C]-DPA-713

“…In fact, it has been shown that venous blood samples may practically be used instead for scaling purpose since arterial and venous blood tend to reach equilibrium at about 30-45 minutes post-injection time (17). Although this was not tested in this work, but similar TSPO studies have also found that PBIF can be appropriately scaled using one blood sample (27,48).…”

“…In this study, the AUC between PSAIF and PBIF was minimized by scaling the PBIF with an arterial blood value at 75minutes, as also recommended by past similar TSPO studies (27,48). Since our goal is to possibly eradicate arterial sampling, a venous sample can potentially be obtained at 75minutes to scale the PBIF for each subject.…”