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

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.

Abbreviations: AEF, amyloid enhancing factor; CR, Congo red; HSPG, heparan sulfate proteoglycan; PET, positron emission tomography; SAA, serum amyloid protein A; SPECT, single photon emission computed tomography

• AA amyloid
• biodistribution
• congo red
• peptides
• tissue amyloid