Publication Date:
2020-11-05
Description:
Background: Systemic immunoglobulin light chain-associated amyloidosis (AL) is a rare disorder associated with the production of monoclonal free light chain proteins. The aggregation of misfolded light chains leads to the extracellular deposition of amyloid fibrils associated with proteoglycans and other serum-derived proteins. Amyloid deposits accumulate in abdominothoracic organs, notably the heart, liver, spleen, kidneys, as well as peripheral nerves. This process results in cytotoxicity and ultimately to organ dysfunction. Presently, there are no radiotracers approved in the US for the quantitative detection and measurement of systemic AL amyloidosis. We have developed a synthetic peptide radiotracer, designated 124I-p5+14 that 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). In 2018, a Phase 1, first-in-human PET imaging study began using 124I-p5+14 in patients with a biopsy-confirmed diagnosis of AL amyloidosis. In addition, patients with other forms of systemic amyloidosis are also being recruited into this ongoing clinical study (NCT 03678259). To date, 30 patients have completed the PET/CT imaging study including 15 subjects with AL amyloidosis. The primary endpoint includes safety and dosimetry estimation with a secondary endpoint of patient- and organ-specific sensitivity of 124I-p5+14. Patients receive follow up contact by study staff on days 9 and 28 for safety and symptom assessment. Here we provide an update on the detection and quantitation of AL amyloid in patients, using 124I-p5+14 PET imaging. Additionally, we present a method, using PET imaging of the radiotracer, for differentiating patients with AL from those with transthyretin-associated (ATTR) amyloidosis. Methods: Patients 〉18 years of age with biopsy-proven amyloidosis with adequate renal function (Cr 〈 1.5 x ULN) and not requiring heparin therapy are eligible. Subjects received
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
,
Medicine
Permalink