title: Quantitative high-resolution microradiographic imaging of amyloid deposits in a novel murine model of AA amyloidosis.
abstract: The mouse model of experimentally induced systemic AA amyloidosis is long established, well validated, and closely analogous to the human form of this disease. However, the induction of amyloid by experimental inflammation is unpredictable, inconsistent, and difficult to modulate. We have previously shown that murine AA amyloid deposits can be imaged using iodine-123 labeled SAP scintigraphy and report here substantial refinements in both the imaging technology and the mouse model itself. In this regard, we have generated a novel prototype of AA amyloid in which mice expressing the human interleukin 6 gene, when given amyloid enhancing factor, develop extensive and progressive systemic AA deposition without an inflammatory stimulus, i.e., a transgenic rapidly inducible amyloid disease (TRIAD) mouse. Additionally, we have constructed high-resolution micro single photon emission computed tomography (SPECT)/computed tomography (CT) instrumentation that provides images revealing the precise anatomic location of amyloid deposits labeled by radioiodinated serum amyloid P component (SAP). Based on reconstructed microSPECT/CT images, as well as autoradiographic, isotope biodistribution, and quantitative histochemical analyses, the (125)I-labeled SAP tracer bound specifically to hepatic and splenic amyloid in the TRIAD animals. The ability to discern radiographically the extent of amyloid burden in the TRIAD model provides a unique opportunity to evaluate the therapeutic efficacy of pharmacologic compounds designed to inhibit fibril formation or effect amyloid resolution.
authors.affiliation: Human Immunology and Cancer Program, Department of Medicine, University of Tennessee Graduate School of Medicine, Knoxville, 37920, USA. jwall@mc.utmck.edu
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Wall
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Kennel
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Paulus
authors.forename: Shaun
authors.initials: S
authors.lastname: Gleason
authors.forename: Jens
authors.initials: J
authors.lastname: Gregor
authors.forename: Justin
authors.initials: J
authors.lastname: Baba
authors.forename: Maria
authors.initials: M
authors.lastname: Schell
authors.forename: Tina
authors.initials: T
authors.lastname: Richey
authors.forename: Brian
authors.initials: B
authors.lastname: O'Nuallain
authors.forename: Robert
authors.initials: R
authors.lastname: Donnell
authors.forename: Philip N
authors.initials: PN
authors.lastname: Hawkins
authors.forename: Deborah T
authors.initials: DT
authors.lastname: Weiss
authors.forename: Alan
authors.initials: A
authors.lastname: Solomon
mesh_terms: D000682:Amyloid / Q000378:metabolism*; D000686:Amyloidosis / Q000175:diagnosis / Q000000981:diagnostic imaging* / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001345:Autoradiography; D004195:Disease Models, Animal; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics; D007457:Iodine Radioisotopes / Q000378:metabolism; D008668:Metallothionein / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic; D011859:Radiography; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D000682:Amyloid; D015850:Interleukin-6; D007457:Iodine Radioisotopes; D008668:Metallothionein