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

Reference tissue methods to estimate neuroreceptor binding are not applicable to [(18)F]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)=K(1)/K'(1)) from [(18)F]FP-TZTP PET data of healthy aged subjects (10 with apolipoprotein E-epsilon4 alleles (APOE-epsilon4(+)) and nine without (APOE-epsilon4(-)). 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-epsilon4(+) 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)() (mins) (1,659+/-497) and V(T) (mL/cm(3)) (701+/-99) in APOE-epsilon4(+) were higher by 38 and 22% than those (1,209+/-233 and 577+/-112) in APOE-epsilon4(-), respectively. The statistical significance for V(T)() (0.041) was lower than that for V(T) (0.025), due to the higher intersubject variability of 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.