Noninvasive bi-graphical analysis for the quantification of slowly reversible radioligand binding

In this paper, we presented a novel reference-region-based (noninvasive) bi-graphical analysis for the quantification of a reversible radiotracer binding that may be too slow to reach relative equilibrium (RE) state during positron emission tomography (PET) scans. The proposed method indirectly implements the noninvasive Logan plot, through arithmetic combination of the parameters of two other noninvasive methods and the apparent tissueto- plasma efflux rate constant for the reference region (k₂). We investigated its validity and statistical properties, by performing a simulation study with various noise levels and k₂ values, and also evaluated its feasibility for [18F] FP-CIT PET in human brain. The results revealed that the proposed approach provides distribution volume ratio estimation comparable to the Logan plot at low noise levels while improving underestimation caused by non-RE state differently depending on k₂. Furthermore, the proposed method was able to avoid noise-induced bias of the Logan plot, and the variability of its results was less dependent on k₂ than the Logan plot. Therefore, this approach, without issues related to arterial blood sampling given a pre-estimate of k2 (e.g. population-based), could be useful in parametric image generation for slow kinetic tracers staying in a non-RE state within a PET scan.