Less invasive quantification of positron emission tomography data using simultaneous estimation of the input function

Objectives: Full quantification of positron emission tomography (PET) data requires arterial blood sampling throughout the scan to determine an arterial input function (AIF), adding cost and risk to PET studies. Simultaneous estimation (SIME) is a less-invasive PET quantification method that recovers the AIF, requiring only a single arterial blood sample. The goal of this study is to determine if a single venous sample can be used instead of the arterial sample used in SIME for the tracers [11C]-ABP688, [11C]-CUMI-101, and [11C]-DASB. Methods: In addition to automated blood sampling, manual venous and arterial plasma activities, parent fractions, and metabolite-corrected plasma activities were acquired for venous-to-arterial comparison at the time-points: 4, 12, 30, 60 minutes for [11C]-ABP688 (N=10 60-minute scans); 30, 60, 90 minutes for [11C]-CUMI-101 (N=19 120-minute scans); and 50, 80, and 100 minutes for [11C]-DASB (N=18 100-minute scans). A two-tissue compartment model was fit for [11C]-ABP688 and likelihood estimation graphical analysis (LEGA) was fit for [11C]-CUMI-101 and [11C]-DASB to generate total distribution volume (V_T) estimates with an AIF and arterial- and venous-SIME generated input functions. Results: In this dataset, venous and arterial metabolite-corrected plasma activities approximated each other at varying times post-injection across the tracers ([11C]-ABP688: 12 minutes; [11C]-CUMI-101: 90 minutes; [11C]-DASB: 100 minutes). Arterial-SIME and venous-SIME derived estimates of V_T closely agreed with AIF estimates for at least one venous and one arterial time-point post injection. The optimal sampling times post injection (defined based on percentage differences from AIF-based V_T) were: [11C]-ABP688: 12 minutes for arterial-SIME and venous-SIME (-8.4 ± 7.4% and -6.1 ± 7.0%), [11C]-CUMI-101: 30 minutes for arterial-SIME and venous-SIME (3.9 ± 7.6% and -14.2 ± 10.4%), and [11C]-DASB: 80 minutes for arterial-SIME and 100-minute venous-SIME (-6.8 ± 8.9% and -9.3 ± 6.5%). Conclusions: A single venous sample with SIME may be an alternative for quantification of [11C]-ABP688, [11C]-CUMI-101, and [11C]-DASB.