In:
Journal of Cerebral Blood Flow & Metabolism, SAGE Publications, Vol. 30, No. 9 ( 2010-09), p. 1608-1618
Abstract:
[ 11 C]PBR28, 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 C]PK11195, another TSPO radioligand. We measured the specific binding signals with [ 3 H]PK11195 and [ 3 H]PBR28 in brain tissue from 22 donors. Overall, 23% of the samples did not generate a visually detectable specific autoradiographic signal with [ 3 H]PBR28, although all samples showed [ 3 H]PK11195 binding. There was a marked reduction in the affinity of [ 3 H]PBR28 for TSPO in samples with no visible [ 3 H]PBR28 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 H]PBR28 bound with a two-site fit in 40% of cases, with affinities ( K i ) of 4.0±2.4 nmol/L (high-affinity site) and 313±77 nmol/L (low-affinity site). There was no difference in K d or B max for [ 3 H]PK11195 in samples showing no [ 3 H]PBR28 autoradiographic signal relative to those showing normal [ 3 H]PBR28 autoradiographic signal. [ 3 H]PK11195 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 C]PBR28 binding may not be interpreted simply as a reduction in TSPO density. The functional significance of differences in binding characteristics warrants further investigation.
Type of Medium:
Online Resource
ISSN:
0271-678X
,
1559-7016
DOI:
10.1038/jcbfm.2010.63
Language:
English
Publisher:
SAGE Publications
Publication Date:
2010
detail.hit.zdb_id:
2039456-1
