title: Noninvasive estimation of normalized distribution volume: application to the muscarinic-2 ligand [(18)F]FP-TZTP.
abstract: 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.
authors.affiliation: Kreitchman PET Center, Department of Radiology, Columbia University College of Physicians, New York, New York 10032, USA. mi2193@columbia.edu
authors.forename: Masanori
authors.initials: M
authors.lastname: Ichise
authors.forename: Robert M
authors.initials: RM
authors.lastname: Cohen
authors.forename: Richard E
authors.initials: RE
authors.lastname: Carson
mesh_terms: D000368:Aged / Q000502:physiology*; D000465:Algorithms; D001057:Apolipoproteins E / Q000235:genetics / Q000502:physiology; D001921:Brain / Q000000981:diagnostic imaging; D003198:Computer Simulation; D005260:Female; D005462:Fluorine Radioisotopes; D006801:Humans; D008297:Male; D015233:Models, Statistical; D017711:Nonlinear Dynamics; D049268:Positron-Emission Tomography; D011725:Pyridines / Q000493:pharmacokinetics; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D043585:Receptor, Muscarinic M2 / Q000235:genetics / Q000502:physiology*; D012015:Reference Standards; D013844:Thiazoles / Q000493:pharmacokinetics
chemical_list: D001057:Apolipoproteins E; D005462:Fluorine Radioisotopes; D011725:Pyridines; D019275:Radiopharmaceuticals; D043585:Receptor, Muscarinic M2; D013844:Thiazoles; C115177:FP-TZTP