Minimally invasive quantification of [¹⁸F]MC225 PET using constrained simultaneous estimation of the input function

[¹⁸F]MC225 is a PET radiotracer used to assess P-glycoprotein function at the bloodbrain barrier. [¹⁸F]MC225 PET quantification requires arterial catheterization to obtain the plasma input function, an invasive procedure. The simultaneous estimation of the input function (SIME) has been proposed as a technique for estimating the plasma input function, however, it requires at least one venous/arterial blood sample. Long axial field-of-view (LAFOV) PET scanners enable a variation of the SIME algorithm, the constrained SIME (cSIME), that incorporates information from whole-blood activity, potentially eliminating the need for blood sampling. In this study, we evaluated the feasibility of cSIME for quantifying the [¹⁸F]MC225 in the brain using a clinical dataset.

Dynamic data from seven subjects scanned on a LAFOV PET system following injection of [¹⁸F]MC225 were included. The constrained SIME method was used to estimate the plasma input function of each subject. A whole-blood input function extracted from the ascending aorta was used as the initial estimate, and multiple brain regions were simultaneously fitted to estimate the parameters required to convert the whole-blood input function into a plasma input function. Volume of distribution (V_T) values were calculated using both the ground-truth and cSIME-estimated plasma input functions with a reversible two-tissue compartment model.

Without a blood sample,V_Testimates using the cSIME plasma input function resulted in relative differences ranging between approximately -26% and 11% compared to theV_Testimates obtained with the measured plasma input function. Incorporating one blood sample as anchor at 60 minutes decrease these relative differences to 11%.

The findings of this study suggest that cSIME may help reduce the invasiveness of quantitative [¹⁸F]MC225 PET studies. The clinical relevance of the observed bias will ultimately depend on its magnitude relative to disease-related differences in kinetic parameters expected in patient populations.