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In vivo evaluation of a novel F-labeled PET radioligand for translocator protein 18 kDa (TSPO) in monkey brain. | LitMetric
Purpose : [F]SF51 was previously found to have high binding affinity and selectivity for 18 kDa translocator protein (TSPO) in mouse brain. This study sought to assess the ability of [F]SF51 to quantify TSPO in rhesus monkey brain.Methods : Positron emission tomography (PET) imaging was performed in monkey brain (n = 3) at baseline and after pre-blockade with the TSPO ligands PK11195 and PBR28. TSPO binding was calculated as total distribution volume corrected for free parent fraction in plasma (V/f) using a two-tissue compartment model. Receptor occupancy and nondisplaceable uptake were determined via Lassen plot. Binding potential (BP) was calculated as the ratio of specific binding to nondisplaceable uptake. Time stability of V was used as an indirect probe to detect radiometabolite accumulation in the brain. In vivo and ex vivo experiments were performed in mice to determine the distribution of the radioligand.Results : After [F]SF51 injection, the concentration of brain radioactivity peaked at 2.0 standardized uptake value (SUV) at ~ 10 min and declined to 30% of the peak at 180 min. V/f at baseline was generally high (203 ± 15 mL· cm) and decreased by ~ 90% after blockade with PK11195. BP of the whole brain was 7.6 ± 4.3. V values reached levels similar to terminal 180-min values by 100 min and remained relatively stable thereafter with excellent identifiability (standard errors < 5%), suggesting that no significant radiometabolites accumulated in the brain. Ex vivo experiments in mouse brain showed that 96% of radioactivity was parent. No significant uptake was observed in the skull, suggesting a lack of defluorination in vivo.Conclusion : The results demonstrate that [F]SF51 is an excellent radioligand that can quantify TSPO with a good ratio of specific to nondisplaceable uptake and has minimal radiometabolite accumulation in brain. Collectively, the results suggest that [F]SF51 warrants further evaluation in humans.
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