Background: This study explores different approaches to estimate the clearance rate of the reference tissue (k'2) parameter used for pharmacokinetic modeling, using the simplified reference tissue model 2 (SRMT2) and further explores the effect on the binding potential (BPND) of 11C-labeled Pittsburgh Compound B (PIB) PET scans. Methods: Thirty subjects underwent a dynamic PIB PET scan and were classified as PIB positive (+) or negative (–). Thirteen regions were defined from where to estimate k'2 : the whole brain, eight anatomical region based on the Hammer's atlas, one region based on a SPM comparison between groups on a voxel level, and three regions using different BPSRTMND thresholds. Results: The different approaches resulted in distinct k'2 estimations per subject. The median value of the estimated k'2 across all subjects in the whole brain was 0.057. In general, PIB+ subjects presented smaller k'2 estimates than this median, and PIB–, larger. Furthermore, only threshold and white matter methods resulted in non-significant differences between groups. Moreover, threshold approaches yielded the best correlation between BPSRTMND and BPSRTM2ND for both groups (R2 = 0.85 for PIB+, and R2 = 0.88 for PIB–). Lastly, a sensitivity analysis showed that overestimating k'2 values resulted in less biased BPSRTM2ND estimates. Conclusion: Setting a threshold on BPSRTMND might be the best method to estimate k'2 in voxel-based modeling approaches, while the use of a white matter region might be a better option for a volume of interest based analysis.
CITATION STYLE
Peretti, D. E., Reesink, F. E., Doorduin, J., de Jong, B. M., De Deyn, P. P., Dierckx, R. A. J. O., … Vállez García, D. (2019). Optimization of the k’2 Parameter Estimation for the Pharmacokinetic Modeling of Dynamic PIB PET Scans Using SRTM2. Frontiers in Physics, 7. https://doi.org/10.3389/fphy.2019.00212
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