Comparison of [11C]-(R)-PK 11195 and [11C]PBR28, two radioligands for translocator protein (18 kDa) in human and monkey: Implications for positron emission tomographic imaging of this inflammation biomarker

Ten percent of humans lack specific binding of [C-11]PBR28 to 18 kDa translocator protein (TSPO), a biomarker for inflammation. Non-binders have not been reported using another TSPO radioligand, [C-11]-(R)-PK 11195, despite its use for more than two decades. This study asked two questions: (1) What is the cause of nonbinding to PBR28? and (2) Why has this phenomenon not been reported using [C-11]-(R)-PK 11195? Methods: Five binders and five non-binders received whole-body imaging with both [C-11]-(R)-PK 11195 and [C-11]PBR28. In vitro binding was performed using leukocyte membranes from binders and non-binders and the tritiated versions of the ligand. Rhesus monkeys were imaged with [C-11]-(R)-PK 11195 at baseline and after blockade of TSPOs. Results: Using [C-11]PBR28, uptake in all five organs with high densities of TSPO (lung, heart, brain, kidney, and spleen) was 50% to 75% lower in non-binders than in binders. In contrast, [C-11]-(R)-PK 11195 distinguished binders and non-binders in only heart and lung. For the in vitro assay, [H-3]PBR28 had more than 10-fold lower affinity to TSPO in non-binders than in binders. The in vivo specific binding of [C-11]-(R)-PK 11195 in monkey brain was similar to 80-fold lower than that reported for [C-11]PBR28. Conclusions: Based on binding of [H-3]PK 11195 to leukocyte membranes, both binders and non-binders express TSPO. Non-binding to PBR28 is caused by its low affinity for TSPO in non-binders. Non-binding may be differentially expressed in organs of the body. The relatively low in vivo specific binding of [C-11]-(R)-PK 11195 may have obscured its detection of nonbinding in peripheral organs. Published by Elsevier Inc.