title: Comparative evaluation of p5+14 with SAP and peptide p5 by dual-energy SPECT imaging of mice with AA amyloidosis.
abstract: Amyloidosis is a protein-misfolding disorder characterized by the extracellular deposition of amyloid, a complex matrix composed of protein fibrils, hyper-sulphated glycosaminoglycans and serum amyloid P component (SAP). Accumulation of amyloid in visceral organs results in the destruction of tissue architecture leading to organ dysfunction and failure. Early differential diagnosis and disease monitoring are critical for improving patient outcomes; thus, whole body amyloid imaging would be beneficial in this regard. Non-invasive molecular imaging of systemic amyloid is performed in Europe by using iodine-123-labelled SAP; however, this tracer is not available in the US. Therefore, we evaluated synthetic, poly-basic peptides, designated p5 and p5+14, as alternative radiotracers for detecting systemic amyloidosis. Herein, we perform a comparative effectiveness evaluation of radiolabelled peptide p5+14 with p5 and SAP, in amyloid-laden mice, using dual-energy SPECT imaging and tissue biodistribution measurements. All three radiotracers selectively bound amyloid in vivo; however, p5+14 was significantly more effective as compared to p5 in certain organs. Moreover, SAP bound principally to hepatosplenic amyloid, whereas p5+14 was broadly distributed in numerous amyloid-laden anatomic sites, including the spleen, liver, pancreas, intestines and heart. These data support clinical validation of p5+14 as an amyloid radiotracer for patients in the US.
authors.affiliation: Department of Medicine, University of Tennessee Graduate School of Medicine, 1924 Alcoa Highway, Knoxville, TN, 37920, USA.
authors.forename: Emily B
authors.initials: EB
authors.lastname: Martin
authors.affiliation: Department of Medicine, University of Tennessee Graduate School of Medicine, 1924 Alcoa Highway, Knoxville, TN, 37920, USA.
authors.forename: Angela
authors.initials: A
authors.lastname: Williams
authors.affiliation: Department of Medicine, University of Tennessee Graduate School of Medicine, 1924 Alcoa Highway, Knoxville, TN, 37920, USA.
authors.forename: Tina
authors.initials: T
authors.lastname: Richey
authors.affiliation: Department of Radiology, and University of Tennessee Graduate School of Medicine, 1924 Alcoa Highway, Knoxville, TN, 37920, USA.
authors.forename: Alan
authors.initials: A
authors.lastname: Stuckey
authors.affiliation: Department of Surgery, University of Tennessee Graduate School of Medicine, 1924 Alcoa Highway, Knoxville, TN, 37920, USA.
authors.forename: R Eric
authors.initials: RE
authors.lastname: Heidel
authors.affiliation: Department of Medicine, University of Tennessee Graduate School of Medicine, 1924 Alcoa Highway, Knoxville, TN, 37920, USA.|Department of Radiology, and University of Tennessee Graduate School of Medicine, 1924 Alcoa Highway, Knoxville, TN, 37920, USA.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Kennel
authors.affiliation: Department of Medicine, University of Tennessee Graduate School of Medicine, 1924 Alcoa Highway, Knoxville, TN, 37920, USA.|Department of Radiology, and University of Tennessee Graduate School of Medicine, 1924 Alcoa Highway, Knoxville, TN, 37920, USA.
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Wall
mesh_terms: D000686:Amyloidosis / Q000000981:diagnostic imaging* / Q000378:metabolism*; D000818:Animals; D004195:Disease Models, Animal; D007457:Iodine Radioisotopes / Q000494:pharmacology; D007553:Isotope Labeling / Q000379:methods; D051379:Mice; D010455:Peptides / Q000493:pharmacokinetics / Q000494:pharmacology; D011849:Radioactive Tracers; D000683:Serum Amyloid P-Component / Q000378:metabolism* / Q000494:pharmacology; D000072098:Single Photon Emission Computed Tomography Computed Tomography / Q000379:methods*
chemical_list: D007457:Iodine Radioisotopes; D010455:Peptides; D011849:Radioactive Tracers; D000683:Serum Amyloid P-Component; C000612168:p5 amyloid-reactive peptide