In:
Journal of Neurochemistry, Wiley, Vol. 102, No. 6 ( 2007-09), p. 2118-2131
Kurzfassung:
Activated microglia are an important feature of many neurological diseases and can be imaged in vivo using 1‐(2‐chlorophenyl)‐ N ‐methyl‐ N ‐(1‐methylpropyl)‐3‐isoquinolinecarboxamide (PK11195), a ligand that binds the peripheral benzodiazepine receptor (PBR). N ‐(2,5‐dimethoxybenzyl)‐ N ‐(5‐fluoro‐2‐phenoxyphenyl) acetamide (DAA1106) is a new PBR‐specific ligand that has been reported to bind to PBR with higher affinity compared with PK11195. We hypothesized that this high‐affinity binding of DAA1106 to PBR will enable better delineation of microglia in vivo using positron emission tomography. [ 3 H]DAA1106 showed higher binding affinity compared with [ 3 H]( R )‐PK11195 in brain tissue derived from normal rats and the rats injected intrastriatally with 6‐hydroxydopamine or lipopolysaccharide at the site of the lesion. Immunohistochemistry combined with autoradiography in brain tissues as well as correlation analyses showed that increased [ 3 H]DAA1106 binding corresponded mainly to activated microglia. Finally, ex vivo autoradiography and positron emission tomography imaging in vivo showed greater retention of [ 11 C]DAA1106 compared with [ 11 C]( R )‐PK11195 in animals injected with either lipopolysaccaride or 6‐hydroxydopamine at the site of lesion. These results indicate that DAA1106 binds with higher affinity to microglia in rat models of neuroinflammation when compared with PK11195, suggesting that [ 11 C]DAA1106 may represent a significant improvement over [ 11 C]( R )‐PK11195 for in vivo imaging of activated microglia in human neuroinflammatory disorders.
Materialart:
Online-Ressource
ISSN:
0022-3042
,
1471-4159
DOI:
10.1111/jnc.2007.102.issue-6
DOI:
10.1111/j.1471-4159.2007.04690.x
Sprache:
Englisch
Verlag:
Wiley
Publikationsdatum:
2007
ZDB Id:
2020528-4
SSG:
12