Small-animal PET study for noninvasive quantification of transmembrane AMPA receptor regulatory protein γ-8 (TARP γ-8) in the brain

Transmembrane AMPA receptor regulatory protein γ-8 (TARP γ-8) mediates various AMPA receptor functions. Recently, [ 11 C]TARP-2105 was developed as a PET ligand for TARP γ-8 imaging. We performed a full kinetic analysis of [ 11 C]TARP-2105 using PET with [ 11 C]TARP-2105 for the first time. The distribution volume ( V T ), which is a macro parameter consisting of the K 1 – k 4 rate constants in the two-tissue compartment model analysis, exhibited the following rank order: hippocampus (1.4 ± 0.3) > amygdala (1.0 ± 0.2) > frontal cortex (0.9 ± 0.2) > striatum (0.8 ± 0.2) ≫ cerebellum (0.5 ± 0.1) ≈ thalamus (0.5 ± 0.1) > pons (0.4 ± 0.1 mL/cm 3 ). These heterogenous V T values corresponded with the order of biological distribution of TARP γ-8 in the brain. To validate the reference tissue model, the binding potential (BP ND ) of [ 11 C]TARP-2105 for TARP γ-8 was estimated using general methods (SRTM, MRTM0, Logan reference model, and ratio method). These BP ND s based on reference models indicated excellent correlation (R 2 > 0.9) to the indirect BP ND s based on 2TCM with moderate reproducibility (%variability ≈ 10). PET with [ 11 C]TARP-2105 enabled noninvasive BP ND estimation and visual mapping of TARP γ-8 in the living rat brain.