Two binding sites for 3 HPBR28 in human brain: Implications for TSPO PET imaging of neuroinflammation

Abstract

11 CPBR28, a radioligand targeting the translocator protein (TSPO), does not produce a specific binding signal in approximately 14% of healthy volunteers. This phenomenon has not been reported for 11 CPK11195, another TSPO radioligand. We measured the specific binding signals with 3 HPK11195 and 3 HPBR28 in brain tissue from 22 donors. Overall, 23% of the samples did not generate a visually detectable specific autoradiographic signal with 3 HPBR28, although all samples showed 3 HPK11195 binding. There was a marked reduction in the affinity of 3 HPBR28 for TSPO in samples with no visible 3 HPBR28 autoradiographic signal (K i 188+15.6 nmol/L), relative to those showing normal signal (K i 3.4+0.5 nmol/L, P=0.001). Of this latter group, 3 HPBR28 bound with a two-site fit in 40% of cases, with affinities (K i) of 4.02.4 nmol/L (high-affinity site) and 31377 nmol/L (low-affinity site). There was no difference in K d or B max for 3 HPK11195 in samples showing no 3 HPBR28 autoradiographic signal relative to those showing normal 3 HPBR28 autoradiographic signal. 3 HPK11195 bound with a single site for all samples. The existence of three different binding patterns with PBR28 (high-affinity binding (46%), low-affinity binding (23%), and two-site binding (31%)) suggests that a reduction in 11 CPBR28 binding may not be interpreted simply as a reduction in TSPO density. The functional significance of differences in binding characteristics warrants further investigation. © 2010 ISCBFM All rights reserved.