In vivo evaluation of a novel 18F-labeled PET radioligand for translocator protein 18kDa (TSPO) in monkey brain

Introduction: A previous study has shown that ¹⁸F-SF12051 has high binding affinity and selectivity for TSPO in mouse brain¹. This study sought to further evaluate the suitability of ¹⁸F-SF12051 for absolute quantification of TSPO in monkey brain.

Methods: PET imaging was performed in monkey brain (n = 3) at baseline and after blockade by the TSPO ligand, PK11195. The concentration of parent radioligand was measured in concurrent arterial blood samples. The TSPO binding was calculated as total distribution volume corrected for free parent fraction in plasma (V_T/f_P) using a two-tissue compartment model (2TCM). Receptor occupancy and nondisplaceable uptake were determined via Lassen plot. Binding potential (BP_ND) was calculated as the ratio of specific binding to nondisplaceable uptake. Time stability of V_T was used as an indirect probe for detection of radiometabolite accumulation in the brain.

Results: After ¹⁸F-SF12051 injection, the concentration of brain radioactivity peaked at 2.0 SUV at ~10 minutes and declined to 30% of the peak at 180 minutes. V_T/f_P at baseline was generally high (190 ± 13 mL· cm^-3) and decreased by ~80% after blocked with PK11195. BP_ND of the whole brain was 7.3 ± 4.5. V_T values reached the similar level of terminal 180-minute values by 70 minutes and remained relatively stable thereafter with excellent identifiability (standard errors < 5%), suggesting that no significant radiometabolites accumulated in the brain.

Conclusions: The results demonstrate that ¹⁸F-SF12051 is an excellent radioligand with a good ratio of specific to nondisplaceable uptake as well as good time stability of total receptor binding. Based on these data, ¹⁸F-SF12051 warrants further evaluation in human.

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