Quantitative comparison of the peripheral benzodiazepine receptor ligands [18F]PBR102 and [18F]PBR111 in baboons with PET

Objectives To evaluate and compare the kinetics of the fluoroethoxy ([¹⁸F]PBR102) and fluoropropoxy ([¹⁸F]PBR111) substituted 2-(6-chloro-2-phenyl)imidazo[1,2-a]pyridine-3-yl)-N,N-diethylacetamides in baboons (Papio Hamadryas).

Methods Dynamic brain imaging studies in baboons were performed with [¹⁸F]PBR102 and [¹⁸F]PBR111 at baseline and with PK11195 (5 mg/kg) pre-blocking prior to tracer administration on a Biograph TruV 64-slice PET-CT scanner. Whole body imaging was performed at the completion of the dynamic data collection. Arterial blood sampling, plasma and metabolite analysis (SPE and HPLC) provided the metabolite-corrected input function. Parametric volume of distribution images (V_d) were generated using the Logan plot.

Results V_d values in brain cortical regions at baseline and after pre-blocking are summarised in the following table:

Results Bone marrow time activity curves displayed the expected specific binding, which could be blocked. Cortical bone uptake due to defluorination was observed with PBR111, but not with PBR102. Whole body imaging showed high uptake in PBR receptor rich tissues, which was blocked by PK11195.

Conclusions [¹⁸F]PBR102 and [¹⁸F]PBR111 show specific binding in PBR rich tissues, which was blocked with PK11195. The kinetics, low non-specific binding and low metabolite uptake in the brain make these tracers suitable for imaging PBR receptor associated cerebral abnormalities.