Head-to-head comparison of ¹¹C-PBR28 and ¹¹C-ER176 for quantification of the translocator protein in the human brain

Introduction: ¹¹C-ER176 is a new PET tracer to quantify the translocator protein (TSPO), a biomarker for inflammation. The aim of this study was to perform a head-to-head comparison between ¹¹C-ER176 and the widely used ¹¹C-PBR28. Methods: Seven healthy volunteers had a 90-min PET scan and metabolite-corrected arterial input function with ¹¹C-PBR28 in the morning and ¹¹C-ER176 in the afternoon. Binding was quantified at the regional level in terms of V_T with a two-tissue compartmental model. By using V_ND values from the literature obtained with pharmacological blockade, we derived the binding potential BP_ND for both tracers. Results: ¹¹C-ER176 was more stable in arterial blood than ¹¹C-PBR28 (the percentages of unmetabolized parent in plasma at 90 min were 29.0 ± 8.3% and 8.8 ± 2.9% respectively). The brain time–activity curves for both tracers were well fitted by the two-tissue model, but ¹¹C-ER176 had higher V_T values than ¹¹C-PBR28 (5.74 ± 1.54 vs 4.43 ± 1.99 ml/cm³) and a lower coefficient of variation. The BP_ND of ¹¹C-ER176 was more than 4 times larger than that of ¹¹C-PBR28 for high-affinity binders, and more than 9 times larger for mixed-affinity binders. Conclusion: ¹¹C-ER176 displays a higher binding potential and a smaller variability of V_T values. Thanks to these characteristics, clinical studies performed with ¹¹C-ER176 are expected to have higher statistical power and thus require fewer subjects.