Development of a minimally invasive simultaneous estimation method for quantifying translocator protein binding with...

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 [¹⁸F]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.

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 [¹⁸F]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.

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 [¹⁸F]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.