Publication Date:
2019-11-13
Description:
Background: Systemic immunoglobulin light chain-associated amyloidosis (AL) is a rare disorder associated with plasma cell dyscrasias and the production of monoclonal free light chain proteins. Pathology results from the extracellular deposition of proteinaceous (amyloid) fibrils in association with proteoglycans and other serum derived proteins. The amyloid accumulates in abdominothoracic organs, notably the heart, liver, spleen, kidneys, as well as peripheral nerves leading to organ dysfunction and significant morbidity. At present, there are no radiotracers approved in the US for the non-invasive quantitative measurement of systemic AL amyloid disease. We have developed a synthetic polybasic peptide radiotracer, designated 124I-p5+14, which has been shown, in preclinical assays, to bind many forms of amyloid, including AL, ATTR, and ALECT2 (Wall, J.S. et al. (2015) Molecules, 20, 7657). The peptide binds, through multivalent electrostatic interactions, to the hypersulfated heparan sulfate glycosaminoglycans and potentially to the fibrillar constituents of amyloid deposits. Using SPECT and PET imaging of murine systemic amyloidosis, we have demonstrated the specific interaction of radioiodinated peptide p5+14 with amyloid in abdominothoracic organs and tissues. No detectable binding of p5+14 with amyloid-free tissues was observed. In light of these data, p5+14 was prepared for a first-in-human PET imaging study using iodine-124-labeled peptide (NCT 03678259). Methods: Patients 〉18 years of age with biopsy proven amyloidosis with adequate renal function and not requiring heparin therapy are eligible. Subjects receive
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
,
Medicine
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