In vivo molecular imaging of peripheral amyloidosis using heparin-binding peptides

摘要: Heparan sulfate proteoglycans (HSPGs) are ubiquitous components of pathologic amyloid deposits in the organs patients with disorders such as Alzheimer's disease or systemic light chain (AL) reactive (AA) amyloidosis. Molecular imaging methods for early detection limited and generally unavailable outside United Kingdom. Therefore, there is an urgent need to develop novel, specific amyloidophilic radiotracers assist diagnosis, prognostication, monitoring response therapy. Amyloid-associated HSPG can be differentiated from found surrounding healthy cells tissues by preferential binding certain HS-reactive single variable fragments therefore, represents a biomarker that targeted specifically appropriate reagents. Using murine model AA amyloidosis, we have examined vivo reactivity seven heparin-binding peptides using photon emission X-ray computed tomographic imaging, microautoradiography, tissue biodistribution measurements. All bound within 1 h post-injection, but extent differed widely, which was evidenced image quality grain density autoradiographs. One radiolabeled peptide liver, spleen, kidney, adrenal, heart, pancreas avidity it observed tomography images late 24 post-injection. In addition, biotinylated form this shown histochemically bind human AA, ALκ, ALλ, transthyretin amyloidosis (ATTR), Aβ sections. These basic recognize both ex potential noninvasive molecular situ.