Quantification of [18F]LBT-999 binding to the dopamine transporter in the rhesus monkey brain with the HRRT system

Methods: Two female rhesus monkeys (Macaca mulatta, 6.25 kg and 9.85 kg) were studied. [F]LBT-999 was administered IV as bolus injection (187–200 MBq, 90.8–251.3 GBq/μmol, mass: 0.2–0.5 mg) and PET measurements were conducted with the HRRT system for 243 min. The metabolite-corrected arterial input function and the plasma free fraction (fP) were measured. ROIs were drawn on the whole brain, caudate, putamen, midbrain, thalamus, and cerebellum after MRI–PET coregistration. Quantification was performed with kinetic analysis with 1-tissue and 2-tissue compartment model (1-TCM and 2-TCM), Logan graphical analysis, and reference tissue methods: 4-parameter reference tissue model (FRTM), simplified reference tissue model (SRTM), Logan non-invasive, and multilinear reference tissue model (MRTM2), using PMOD3.0. Outcome measures were: BPF (ml cm)=VT−VND/ fP and BPND=VT−VND/VND. The cerebellum was considered as the reference region for the estimation of VND.