Journal
NEUROBIOLOGY OF DISEASE
Volume 29, Issue 2, Pages 232-241Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.nbd.2007.08.016
Keywords
peripheral benzodiazepine receptor; macrophages; PET; DAA1106; HIV encephalitis; PK11195; SIV encephalitis
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Funding
- NCRR NIH HHS [S10 RR014772-018202] Funding Source: Medline
- NIA NIH HHS [R21 AG025829-02, R21 AG025829, R21 AG025829-01] Funding Source: Medline
- NIMH NIH HHS [R01 MH064921-03, K24 MH001717-10, K24 MH01717, R01 MH071151-03, R01 MH071151, K24 MH001717, R01 MH071151-04S1, R01 MH064921-02, R01 MH064921, K24 MH001717-08, R01 MH64921, K24 MH001717-09] Funding Source: Medline
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HIV encephalitis (HIVE) is characterized by neurodegeneration mediated by toxins derived from infected and activated brain macrophages. Since the peripheral benzodiazepine receptor (PBR) is abundant on brain macrophages, we hypothesized that [H-3]DAA1106, a new PBR ligand, can label infected and activated brain macrophages in HIVE. Using cell culture and postmortem brain tissues from HIVE and a macaque model of HIVE, we show that [H-3]DAA1106 binds with high affinity to activated and infected macrophages in regions of synaptic damage. Further, binding affinity reflected by lower K-D (dissociation constant) values and the B-max (total number of binding sites) to K-D ratios reflective of ligand-binding potential was significantly higher with [3H]DAA1106 compared to the extensively characterized PBR ligand [H-3](R)-PK11195. These data suggest that DAA1106 binds with high affinity to activated and infected brain macrophages and possesses binding characteristics beneficial for in vivo use in the detection and clinical monitoring of HIVE using positron emission tomography. (C) 2007 Elsevier Inc. All rights reserved.
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