A novel method for quantifying peripheral tissue amyloid load by using the radiolabeled amyloidophilic peptide, p5

Amyloid. 2013 Mar;20(1):21-6. doi: 10.3109/13506129.2012.757216. Epub 2013 Jan 17.

Abstract

Quantitation of peripheral amyloid deposits by non-invasive molecular imaging can be useful for diagnosis, prognostication and monitoring response to therapy. In order to obtain reliable quantitative data, it is necessary to show a linear positive correlation between the uptake of the molecular probe and the tissue amyloid load. The transgenic H-2/IL-6 mouse model of AA amyloidosis was used to generate animals with varied stages of visceral amyloid disease. The mice were injected with 125I-labeled peptide p5 and tissues analyzed 2 h post-injection using Congo red (CR) staining, radioisotope biodistribution and micro-autoradiography (ARG). Micro-ARG confirmed that 125I-p5 was deposited at all amyloid deposits and sites of Congophilia but not at amyloid-free sites within the tissues evaluated. Furthermore, biodistribution studies revealed that the amount of 125I deposited in liver and spleen correlated with the amount of CR birefringence (expressed as 0-4+ or as tissue area [µm2]) in these tissues with correlation coefficients of r > 0.7 (p < 10(-6)). Deposition of 125I-p5 is a quantitative measure of the amount of AA amyloid in liver and spleen in this mouse model. The p5 peptide has potential as a quantitative amyloid imaging agent in human disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Amyloid / analysis*
  • Amyloidosis / metabolism*
  • Amyloidosis / pathology
  • Animals
  • Iodine Radioisotopes
  • Liver / metabolism*
  • Liver / pathology
  • Mice
  • Mice, Transgenic
  • Molecular Sequence Data
  • Nerve Tissue Proteins / metabolism
  • Nerve Tissue Proteins / pharmacokinetics*
  • Peptide Fragments / metabolism
  • Peptide Fragments / pharmacokinetics*
  • Spleen / metabolism*
  • Spleen / pathology

Substances

  • Amyloid
  • Iodine Radioisotopes
  • Nerve Tissue Proteins
  • Peptide Fragments
  • p5 protein, human