Noninvasive Imaging of Peripherally Injected Alzheimer's Disease Type Synthetic Aβ Amyloid In Vivo

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...

Full description

Saved in:
Bibliographic Details
Published in:Bioconjugate chemistry 2002-03, Vol.13 (2), p.276-284
Main Authors: Marshall, Jeffrey R, Stimson, Evelyn R, Ghilardi, Joseph R, Vinters, Harry V, Mantyh, Patrick W, Maggio, John E
Format: Article
Language:English
Subjects:
Alzheimer Disease - metabolism
Amino Acid Sequence
Amyloid beta-Peptides - administration & dosage
Amyloid beta-Peptides - blood
Amyloid beta-Peptides - chemical synthesis
Amyloid beta-Peptides - pharmacokinetics
Animals
Brain - metabolism
Half-Life
Humans
Indium Radioisotopes
Molecular Sequence Data
Muscle, Skeletal - metabolism
Pentetic Acid - chemistry
Rats
Rats, Sprague-Dawley
Staining and Labeling
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:1043-1802
1520-4812
DOI:10.1021/bc010066z