Comparison of four ¹¹C-labeled PET ligands to quantify translocator protein 18 kDa (TSPO) in human brain: (R)-PK11195, PBR28, DPA-713, and ER176-based on recent publications that measured specific-to-non-displaceable ratios

Translocator protein (TSPO) is a biomarker for detecting neuroinflammation by PET. ¹¹C-(R)-PK11195 has been used to image TSPO since the 1980s. Here, we compared the utility of four ¹¹C-labeled ligands-(R)-PK11195, PBR28, DPA-713, and ER176-to quantify TSPO in healthy humans. For all of these ligands, BP _ND (specific-to-non-displaceable ratio of distribution volumes) was measured by partially blocking specific binding with XNBD173 administration. In high-affinity binders, DPA-713 showed the highest BP _ND of 7.3 followed by ER176 (4.2), PBR28 (1.2), and PK11195 (0.8). Only ER176 allows the inclusion of low-affinity binders because of little influence of radiometabolites and high BP _ND. If inclusion of all three genotypes is important for study logistics, ER176 is the best of these four radioligands for studying neuroinflammation.