title: Dynamic PET and SPECT imaging with radioiodinated, amyloid-reactive peptide p5 in mice: a positive role for peptide dehalogenation.
abstract: Dynamic molecular imaging provides bio-kinetic data that is used to characterize novel radiolabeled tracers for the detection of disease. Amyloidosis is a rare protein misfolding disease that can affect many organs. It is characterized by extracellular deposits composed principally of fibrillar proteins and hypersulfated proteoglycans. We have previously described a peptide, p5, which binds preferentially to amyloid deposits in a murine model of reactive (AA) amyloidosis. We have determined the whole body distribution of amyloid by molecular imaging techniques using radioiodinated p5. The loss of radioiodide from imaging probes due to enzymatic reaction has plagued the use of radioiodinated peptides and antibodies. Therefore, we studied iodine-124-labeled p5 by using dynamic PET imaging of both amyloid-laden and healthy mice to assess the rates of amyloid binding, the relevance of dehalogenation and the fate of the radiolabeled peptide. Rates of blood pool clearance, tissue accumulation and dehalogenation of the peptide were estimated from the images. Comparisons of these properties between the amyloid-laden and healthy mice provided kinetic profiles whose differences may prove to be indicative of the disease state. Additionally, we performed longitudinal SPECT/CT imaging with iodine-125-labeled p5 up to 72h post injection to determine the stability of the radioiodinated peptide when bound to the extracellular amyloid. Our data show that amyloid-associated peptide, in contrast to the unbound peptide, is resistant to dehalogenation resulting in enhanced amyloid-specific imaging. These data further support the utility of this peptide for detecting amyloidosis and monitoring potential therapeutic strategies in patients.
authors.affiliation: Department of Medicine, University of Tennessee Medical Center, 1924 Alcoa Highway, Knoxville, TN 37920, United States. Electronic address: emarti15@vols.utk.edu.
authors.forename: Emily B
authors.initials: EB
authors.lastname: Martin
authors.affiliation: Department of Medicine, University of Tennessee Medical Center, 1924 Alcoa Highway, Knoxville, TN 37920, United States; Department of Radiology, University of Tennessee Medical Center, 1924 Alcoa Highway, Knoxville, TN 37920, United States. Electronic address: skennel@utmck.edu.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Kennel
authors.affiliation: Department of Medicine, University of Tennessee Medical Center, 1924 Alcoa Highway, Knoxville, TN 37920, United States. Electronic address: trichey@utmck.edu.
authors.forename: Tina
authors.initials: T
authors.lastname: Richey
authors.affiliation: Department of Medicine, University of Tennessee Medical Center, 1924 Alcoa Highway, Knoxville, TN 37920, United States. Electronic address: dwooliver@utmck.edu.
authors.forename: Craig
authors.initials: C
authors.lastname: Wooliver
authors.affiliation: Department of Radiology, University of Tennessee Medical Center, 1924 Alcoa Highway, Knoxville, TN 37920, United States. Electronic address: dosborne@utmck.edu.
authors.forename: Dustin
authors.initials: D
authors.lastname: Osborne
authors.affiliation: Department of Medicine, University of Tennessee Medical Center, 1924 Alcoa Highway, Knoxville, TN 37920, United States. Electronic address: awilliams@utmck.edu.
authors.forename: Angela
authors.initials: A
authors.lastname: Williams
authors.affiliation: Department of Radiology, University of Tennessee Medical Center, 1924 Alcoa Highway, Knoxville, TN 37920, United States. Electronic address: astuckey@utmck.edu.
authors.forename: Alan
authors.initials: A
authors.lastname: Stuckey
authors.affiliation: Department of Medicine, University of Tennessee Medical Center, 1924 Alcoa Highway, Knoxville, TN 37920, United States; Department of Radiology, University of Tennessee Medical Center, 1924 Alcoa Highway, Knoxville, TN 37920, United States. Electronic address: jwall@utmck.edu.
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Wall
mesh_terms: D000682:Amyloid / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D054879:Halogenation; D007457:Iodine Radioisotopes; D051379:Mice; D008807:Mice, Inbred BALB C; D057054:Molecular Imaging; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism; D049268:Positron-Emission Tomography; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D000682:Amyloid; D007457:Iodine Radioisotopes; D010446:Peptide Fragments
keywords: Amyloid imaging; Dehalogenation; Dynamic PET imaging; Peptide radiotracer; SPECT
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