Detection of cardiac amyloidosis by PET/CT imaging using 124I-p5+14 peptide

Abstract Introduction Systemic amyloidosis is characterized by the deposition of protein fibrils in abdominothoracic organs, notably the heart, leading to organ dysfunction and significant morbidity. Patients who present with light chain (AL) amyloid-associated cardiomyopathy have a poor prognosis and median survival of only ∼ 9 mos. Cardiac amyloidosis is also present in many of the other forms of the disease and may be ever present in patients with transthyretin-associated amyloidosis (ATTR). Currently, no radiotracers are approved for the quantitative imaging of cardiac amyloid load. To address these needs, we have developed a synthetic amyloid-reactive peptide radiotracer, 124I-p5+14, suitable for PET/CT imaging. The peptide binds the three major forms of amyloid (AL, ATTR and ALECT2), as well as other, less common, types through multivalent electrostatic interactions with amyloid-associated glycosaminoglycans and fibrils. Herein we report safety, dosimetry, and efficacy data on the first 22 patients from the ongoing Phase 1, first-in-human trial of 124I-p5+14 in patients with systemic amyloidosis (NCT 03678259). Methods Patients >18 years of age with a confirmed diagnosis of systemic amyloidosis and not requiring heparin therapy are eligible. Subjects received