Development of a minimally invasive simultaneous estimation method for quantifying translocator protein binding with [ 18 F]FEPPA positron emission tomography

Background The purpose of this study was to assess the feasibility of using a minimally invasive simultaneous estimation method (SIME) to quantify the binding of the 18-kDa translocator protein tracer [ 18 F]FEPPA. Arterial sampling was avoided by extracting an image-derived input function (IDIF) that was metabolite-corrected using venous blood samples. The possibility of reducing scan duration to 90 min from the recommended 2–3 h was investigated by assuming a uniform non-displaceable distribution volume ( V ND ) to simplify the SIME fitting. Results SIME was applied to retrospective data from healthy volunteers and was comprised of both high-affinity binders (HABs) and mixed-affinity binders (MABs). Estimates of global V ND and regional total distribution volume ( V T ) from SIME were not significantly different from values obtained using a two-tissue compartment model (2CTM). Regional V T estimates were greater for HABs compared to MABs for both the 2TCM and SIME, while the SIME estimates had lower inter-subject variability (41 ± 17% reduction). Binding potential (BP ND ) values calculated from regional V T and brain-wide V ND estimates were also greater for HABs, and reducing the scan time from 120 to 90 min had no significant effect on BP ND . The feasibility of using venous metabolite correction was evaluated in a large animal model involving a simultaneous collection of arterial and venous samples. Strong linear correlations were found between venous and arterial measurements of the blood-to-plasma ratio and the remaining [ 18 F]FEPPA fraction. Lastly, estimates of BP ND and the specific distribution volume (i.e., V S = V T − V ND ) from a separate group of healthy volunteers (90 min scan time, venous-scaled IDIFs) agreed with estimates from the retrospective data for both genotypes. Conclusions The results of this study demonstrate that accurate estimates of regional V T , BP ND and V S can be obtained by applying SIME to [ 18 F]FEPPA data. Furthermore, the application of SIME enabled the scan time to be reduced to 90 min, and the approach worked well with IDIFs that were scaled and metabolite-corrected using venous blood samples.