Quantification of Positron Emission Tomography Data Using Simultaneous Estimation of the Input Function: Validation with Venous Blood and Replication of Clinical Studies

Purpose: To determine if one venous blood sample can substitute full arterial sampling in quantitative modeling for multiple positron emission tomography (PET) radiotracers using simultaneous estimation of the input function (SIME).

Procedures: Participants underwent PET imaging with [¹¹C]ABP688, [¹¹C]CUMI-101, and [¹¹C]DASB. Full arterial sampling and additional venous blood draws were performed for quantification with the arterial input function (AIF) and SIME using one arterial or venous (vSIME) sample.

Results: Venous and arterial metabolite-corrected plasma activities were within 6 % of each other at varying time points. vSIME- and AIF-derived outcome measures were in good agreement, with optimal sampling times of 12 min ([¹¹C]ABP688), 90 min ([¹¹C]CUMI-101), and 100 min ([¹¹C]DASB). Simulation-based power analyses revealed that SIME required fewer subjects than the AIF method to achieve statistical power, with significant reductions for [¹¹C]CUMI-101 and [¹¹C]DASB with vSIME. Replication of previous findings and test-retest analyses bolstered the simulation analyses.

Conclusions: We demonstrate the feasibility of AIF recovery using SIME with one venous sample for [¹¹C]ABP688, [¹¹C]CUMI-101, and [¹¹C]DASB. This method simplifies PET acquisition while allowing for fully quantitative modeling, although some variability and bias are present with respect to AIF-based quantification, which may depend on the accuracy of the single venous blood measurement.