Abstract
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Objectives [18F]FEPPA, [18F]PBR06 and [18F]PBR111 are ligands with potential utility for imaging the 18 kDa translocator protein (TSPO, a.k.a., PBR) using PET. The aim of this study is to compare the TSPO binding of these ligands in the baboon brain.
Methods Thirteen scans of 4-6 h duration were performed on 3 isoflurane-anesthetized baboons on the HR+ scanner with the 3 ligands. Studies were performed under baseline conditions, following pre-block, or displacement, with PK11195. Metabolite-corrected arterial input functions and brain time-activity curves were generated for modeling analysis. Total volumes of distribution (VT) were determined, and baseline and pre-block values were compared to assess the magnitude of specific binding.
Results Modeling analysis of displacement data was not reliable due to dramatic changes in the input function, post PK11195. FEPPA was rapidly metabolized, with <5% parent in plasma by 30 min. Conversely, its brain kinetics were very slow, with VT >500 mL/cm3. Metabolism of PBR06 and PBR111 was less rapid, with 5-10% parent at 120 min. A two-tissue model fit the data for both ligands well with VT values of ~50 for PBR06 and ~30 for PBR111. Inter-regional variation was small. Pre-blocking (7 mg/kg) produced reductions in VT of 80-90% for PBR06 and PBR111. Skull activity was visualized in the preblocking scans, suggestive of defluorination. Time analysis of VT values showed increases of 2-5 mL/cm3 from 2 to 4 h, potentially due to uptake of metabolites. These 2 factors had larger effects for PBR111 as a percent of brain activity.
Conclusions Our studies suggest PBR06 has the best profile of the 3 ligands. PBR111 may also be used to quantify brain TSPO binding, but accurate quantification of FEPPA may be problematic. These non-human primate data must be confirmed in humans to determine if inter-species differences affect our conclusion