Imaging brain amyloid of Alzheimer disease In Vivo in transgenic mice with an Aβ peptide radiopharmaceutical

Jeong Lee Hwa, Yun Zhang, Chunni Zhu, Karen Duff, William M. Pardridge

Research output: Contribution to journalArticlepeer-review

77 Scopus citations

Abstract

1-40 is a potential peptide radiopharmaceutical that could be used to image the brain Aβ amyloid of Alzheimer disease in vivo, should this peptide be made transportable through the blood-brain barrier in vivo. The blood-brain barrier transport of [125I]-Aβ1-40 in a transgenic mouse model was enabled by conjugation to the rat 8D3 monoclonal antibody to the mouse transferrin receptor. The Aβ1-40-8D3 conjugate is a bifunctional molecule that binds the blood-brain barrier TfR and undergoes transport into brain and binds the Aβ amyloid plaques of Alzheimer disease. AppSW/Psenl double-transgenic and littermate control mice were administered either unconjugated Aβ1-40 or the Aβ1-40-8D3 conjugate intravenously, and brain scans were obtained 6 hours later. Immunocytochemical analysis showed abundant Aβ immunoreactive plaques in the brains of the AppSW/Psenl transgenic mice and there was a selective retention of radioactivity in the brains of these mice at 6 hours after intravenous administration of the conjugate. In contrast, there was no selective sequestration either of the conjugate in control littermate mouse brain or of unconjugated Aβ1-40 in transgenic mouse brain. In conclusion, the results show that it is possible to image the Aβ amyloid burden in the brain in vivo with an amyloid imaging agent, provided the molecule is conjugated to a blood-brain barrier drug-targeting system.

Original languageEnglish
Pages (from-to)223-231
Number of pages9
JournalJournal of Cerebral Blood Flow and Metabolism
Volume22
Issue number2
DOIs
StatePublished - 2002

Keywords

  • Alzheimer disease
  • Amyloid
  • Blood-brain barrier
  • Drug targeting
  • Monoclonal antibody

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