Neuroimaging PET tracers: An atlas based approach for comparison in NHP PET/CT

Objectives As neuroscience increasingly uses PET agents to evaluate neural pathways, we realized that systematic characterization of the uptake characteristics of innovative tracers would be helpful. To demonstrate the benefit of an atlas based approach and to collect reference data for future preclinical trials, we compared three targeted PET agents to 18F-FDG in healthy non-human primate (NHP) subjects.

Methods Brain PET/CT were acquired using a 64 slice time of flight PET/CT system (Gemini 64 TOF, Philips Healthcare, Cleveland) wrapped and prepared for NHPs. The protocol included continuous dynamic list mode acquisition, allowing rebinning at any desired temporal resolution. Four tracers were evaluated: 18F-FDG, to visualize glucose metabolism; 18F-AV-133, to target the vesicular monoamine transporter 2; 18F-FDOPA, a substrate for the enzyme that converts L-DOPA to dopamine; 68Ga-DOTA-TATE, a somatostatin analog. NHP neuroanatomy segmentation was established using the BrainInfo website. Blinded region of interest (ROI) analysis was performed.

Results The atlas based approach enabled a systematic characterization of tracer uptakes. 18F-FDG displayed strong uptake in both cerebral cortex and striatum. 18F-AV-133 showed increased uptake in the striatum, hypothalamus and substantia nigra compared to cortex. 18F-FDOPA demonstrated more uptake in striatum than in cortex. 68Ga-DOTA-TATE exhibited very low intracranial uptake, as expected in healthy subjects.

Conclusions Qualitative and quantitative comparison of multiple targeted PET neuroimaging tracers in brain PET/CT is feasible using clinical imaging systems and matching ROIs with a reference atlas. Preclinical trials using a similar approach will facilitate optimization of methods for translational neuro-modulation, neuro-functional, and neuro-degenerative imaging and, eventually, patient care.

Research Support This project was supported by the ODOD TECH 10-012, the Wright Center of Innovation, and Battelle Memorial Institute.