title: Development and evaluation of agents for targeting visceral amyloid.
abstract: Wall, JS, Solomon A, Kennel, SJ. Development and evaluation of agents for targeting visceral amyloid. Visceral amyloidosis is a rare disease characterized by the deposition in organs and tissues of protein fibrils, heparan sulfate proteoglycan as well as serum amyloid P component and other serum proteins. Imaging these pathologic deposits aids in the clinical management of patients with amyloidosis. Whole body scintigraphic imaging of amyloid load as well as organ specific anatomic imaging provides information that can inform prognosis and can be used to monitor disease progression or response to therapy. These capabilities are limited in the USA, which has led to our development and evaluation of two new reagents that specifically target amyloidin vivoand have been used to image visceral deposits in mice and patients with AL amyloidosis. The fibril-reactive mAb 11-1F4, when labeled with iodine-124 was shown to bind AL amyloid in patients by using PET/CT imaging. These studies were performed to support the evaluation of this reagent as a novel immunotherapy for AL patients. In addition, we have identified a heparin-binding peptide that co-localizes with murine AA amyloidin vivoand can be used to image the deposits. The interaction of this peptide, designated p5, with amyloid is dependent on the net positive charge and truncated forms that would be more desirable as clinical imaging agents were found to be significantly less efficient for amyloid imaging. The development and positive preclinical validation of these two reagents offers potential new therapeutic and diagnostic tools for patients with these devastating diseases.
authors.affiliation: Departments of Radiology University of Tennessee Graduate School of Medicine, 1924 Alcoa Highway, Knoxville, TN 37920, USA ; Departments of Medicine, University of Tennessee Graduate School of Medicine, 1924 Alcoa Highway, Knoxville, TN 37920, USA.
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Wall
authors.forename: Alan
authors.initials: A
authors.lastname: Solomon
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Kennel