Noninvasive imaging of peripherally injected Alzheimer's disease type synthetic Aβ amyloid in vivo

Jeffrey R. Marshall, Evelyn R. Stimson, Joseph R. Ghilardi, Harry V. Vinters, Patrick W. Mantyh, John E. Maggio

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

The pathological hallmark of Alzheimer's disease (AD) is accumulation in the brain of amyloid composed of the 40-mer peptide Aβ. Many fundamental questions about the biology of (AD) remain unanswered because there is currently no method of quantifying Aβ amyloid in vivo. A noninvasive method of detecting and quantifying Aβ amyloid in vivo would have wide application for the premortem diagnosis of AD and the efficient evaluation of candidate therapeutics aimed at inhibiting the formation and growth of Aβ amyloid. Taking advantage of the extraordinarily high affinity of Aβ for itself, we have synthesized an N′-terminal diethylenetriaminepentaacetic acid (DTPA) derivative of Aβ possessing the kinetic activity and specificity for Aβ amyloid desired of a probe to be used for noninvasive imaging. DTPA-Aβ(3-40) is readily labeled with 111InOAc3 to yield a stable probe with exquisite specificity for naturally occurring and synthetic Aβ amyloid in vitro. Moreover, 111In-DTPA-Aβ(3-40), administered intravascularly can specifically deposit onto and label previously injected synthetic Aβ amyloid and be imaged in vivo with a γ camera. The present results demonstrate the design, synthesis, and use of an Aβ amyloid-specific probe and methods for its use as a noninvasive imaging agent. In vivo imaging of Aβ amyloid represents an important step toward the development of biochemically based objective tools for the assessment of progression of AD and efficacy of potential therapeutics.

Original languageEnglish (US)
Pages (from-to)276-284
Number of pages9
JournalBioconjugate Chemistry
Volume13
Issue number2
DOIs
StatePublished - Apr 13 2002
Externally publishedYes

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Biomedical Engineering
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry

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