Noninvasive estimation of normalized distribution volume:: application to the muscarinic-2 ligand [18F]FP-TZTP

Reference tissue methods to estimate neuroreceptor binding are not applicable to [F-18]FP-TZTP (a muscarinic-2 cholinergic receptor ligand), because there is no suitable receptor-free reference region. We evaluated a new method to estimate, without using arterial data or a receptor-free reference region, a receptor parameter called the normalized distribution volume, V-T*, using a region containing receptors as the input tissue. V-T* is defined as V-T/K-1' (distribution volume (V-T) normalized by K-1' of the input region). We used a two-parameter multilinear reference tissue model (MRTM2) to generate parametric images of V-T* and R-1 (R-1 = K1/K1') from [F-18]FP-TZTP PET data of healthy aged subjects (10 with apolipoprotein E-epsilon 4 alleles (APOE-epsilon 4(+)) and nine without (APOE-epsilon 4(-)). V-T* and V-T were normalized by plasma-free fraction, f(p). By one-tissue kinetic analysis (1TKA) with metabolite-corrected plasma data, V-T was previously reported as higher in the APOE-epsilon 4(+) group. The noise magnitude of MRTM2 V-T* and R-1 images were nearly identical to those of 1TKA V-T and K-1 images. K-1' or f(p) was not different between the two groups. V-T* and R-1 images were nearly identical to those of 1TKA V-T and K-1 images. K-1' or f(p) was not different between the two groups. V-T* (mins) (1,659+/-497) and V-T (mL/cm(3)) (701+/-99) in APOE-epsilon 4(+) were higher by 38 and 22% than those (1,209+/-233 and 577+/-112) in APOE-epsilon 4(-), respectively. The statisticcal significance for V-T* (25%) than that of V-T (17%). We conclude that MRTM2 V-T* allows detection of group differences in receptor binding without arterial blood or a receptor-free reference region.