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

Abstract

Reference tissue methods to estimate neuroreceptor binding are not applicable to [18F]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, VT*, using a region containing receptors as the input tissue. VT* is defined as VT/ K′1 (distribution volume (VT) 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 R1 (R1=K1/ K′1) from [18F]FP-TZTP PET data of healthy aged subjects (10 with apolipoprotein E-ε4 alleles (APOE-ε4(+)) and nine without (APOE-ε4(-)). VT* and VT were normalized by plasma-free fraction, fP. By one-tissue kinetic analysis (1TKA) with metabolite-corrected plasma data, VT was previously reported as higher in the APOE-ε4(+) group. The noise magnitude of MRTM2 VT* and R1 images were nearly identical to those of 1TKA VT and K1 images. K′1 or fP was not different between the two groups. VT* (mins) (1,659±497) and VT (mL/cm3) (701±99) in APOE-ε4(+) were higher by 38 and 22% than those (1,209±233 and 577±112) in APOE-ε4(-), respectively. The statistical significance for VT* (0.041) was lower than that for VT (0.025), due to the higher intersubject variability of VT* (25%) than that of VT (17%). We conclude that MRTM2 VT* allows detection of group differences in receptor binding without arterial blood or a receptor-free reference region. © 2008 ISCBFM All rights reserved.