Journal of Molecular Neuroscience

, Volume 19, Issue 1–2, pp 11–16 | Cite as

Synthesis and evaluation of 2-(3′-lodo-4′-aminophenyl)-6-hydroxybenzothiazole for in vivo quantitation of amyloid deposits in alzheimer’s disease

  • Yanming Wang
  • William E. Klunk
  • Guo-Feng Huang
  • Manik L. Debnath
  • Daniel P. Holt
  • Chester A. Mathis
Early Detection Of Cognitive Impairment

Abstract

A potent and brain permeable amyloid ligand has been identified as a lead compound capable of I-123/125-labelling for single photon emission computed tomography (SPECT) imaging. In this study, we report the synthesis and I-125-radiolabelling of Compound 6 and its in vitro and in vivo properties. Compound 6 [2-(3′-iodo-4′-aminophenyl)-6-hydroxybenzothiazole] bound to synthetic Aβ(1–40) fibrils in a saturable manner, exhibiting an affinity (Ki) of 11±1.1 nM in a competitive binding assay using a tritiated thioflavin T analog ([3H]BTA-1) as radioligand. [125I]6 binding to synthetic Aβ(1–40) fibrils fit a single-site model. [125I]6 exhibited several-fold higher binding to homogenates of frontal cortex from post-mortem Alzheimer’s disease brain relative to age-matched control brain homogenates. No difference in binding was observed in cerebellum. The ratio of radioactivity concentration between frontal cortex and cerebellum was 6-fold higher in AD brain homogenates than the age-matched control. [125I]6 also readily penetrated the blood-brain barrier in normal control mice with an average radioactivity concentration of 6.43 ± 0.62%ID/g detected in the whole brain at 2 min post i.v. injection. At 30 min, the radioactivity concentration decreased to 0.40 ± 0.05%ID/g, indicating good clearance in the absence of amyloid deposits in the brain.

Index Entries

Radiopharmaceuticals Alzheimer’s disease amyloid SPECT 

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Copyright information

© Humana Press Inc 2002

Authors and Affiliations

  • Yanming Wang
    • 1
  • William E. Klunk
    • 2
  • Guo-Feng Huang
    • 1
  • Manik L. Debnath
    • 2
  • Daniel P. Holt
    • 1
  • Chester A. Mathis
    • 1
  1. 1.PET Facility, Department of Radiology, Western Psychiatric Institute and Clinic, School of MedicineUniversity of PittsburghPittsburgh
  2. 2.Department of Psychiatry, Western Psychiatric Institute and Clinic, School of MedicineUniversity of PittsburghPittsburgh

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