title: Tc-99m Radiolabeled Peptide p5 + 14 is an Effective Probe for SPECT Imaging of Systemic Amyloidosis.
abstract: Systemic peripheral amyloidosis is a rare disease in which misfolded proteins deposit in various organs. We have previously developed I-124 labeled peptide p5 + 14 as a tracer for positron emission tomography imaging of amyloid in patients. In this report, we now document the labeling efficiency, bioactivity, and stability of Tc-99m labeled p5 + 14 for single-photon emission computed tomography (SPECT) imaging of amyloidosis, validated in a mouse model of systemic amyloidosis.
  
  
  
  Radiochemical yield, purity, and biological activity of [(99m)Tc]p5 + 14 were documented by instant thin-layer chromatography (ITLC), SDS-PAGE and a quantitative amyloid fibril pulldown assay. The efficacy and stability were documented in serum amyloid protein A (AA) amyloid-bearing or wild-type (WT) control mice imaged with SPECT/X-ray computed tomography (CT) at two time points. The uptake and retention of [(99m)Tc]p5 + 14 in hepatosplenic amyloid was evaluated using region of interest (ROI) and tissue counting measurements.
  
  
  
  Tc-99m p5 + 14 was produced with a radiochemical yield of 75 % with greater than 90 % purity and biological activity comparable to that of radioiodinated peptide. AA amyloid was visualized by SPECT/CT imaging with specific uptake seen in amyloid-laden organs at levels ∼5 folds higher than in healthy mice. ROI analyses of decay-corrected SPECT/CT images showed <20 % loss of radiolabel from the 1 to 4 h imaging time points. Biodistribution data confirmed the specificity of the probe accumulation by amyloid-laden organs as compared to non-diseased tissues.
  
  
  
  [(99m)Tc]p5 + 14 is a specific and stable radiotracer for systemic amyloid in mice and may provide a convenient and inexpensive alternative to imaging of peripheral amyloidosis in patients.
authors.affiliation: Department of Medicine, University of Tennessee, Graduate School of Medicine, Knoxville, TN, USA. skennel@utmck.edu.|Department of Radiology, University of Tennessee, Graduate School of Medicine, Knoxville, TN, USA. skennel@utmck.edu.|University of Tennessee Medical Center, 1924 Alcoa Highway, Knoxville, TN, 37920, USA. skennel@utmck.edu.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Kennel
authors.affiliation: Department of Radiology, University of Tennessee, Graduate School of Medicine, Knoxville, TN, USA.
authors.forename: Alan
authors.initials: A
authors.lastname: Stuckey
authors.affiliation: Department of Medicine, University of Tennessee, Graduate School of Medicine, Knoxville, TN, USA.
authors.forename: Helen P
authors.initials: HP
authors.lastname: McWilliams-Koeppen
authors.affiliation: Department of Medicine, University of Tennessee, Graduate School of Medicine, Knoxville, TN, USA.
authors.forename: Tina
authors.initials: T
authors.lastname: Richey
authors.affiliation: Department of Medicine, University of Tennessee, Graduate School of Medicine, Knoxville, TN, USA.|Department of Radiology, University of Tennessee, Graduate School of Medicine, Knoxville, TN, USA.
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Wall
mesh_terms: D000686:Amyloidosis / Q000000981:diagnostic imaging*; D000818:Animals; D006801:Humans; D000075363:Immunoglobulin Light-chain Amyloidosis; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D010455:Peptides / Q000737:chemistry*; D019275:Radiopharmaceuticals / Q000737:chemistry*; D013667:Technetium / Q000737:chemistry*; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*; D014057:Tomography, X-Ray Computed
chemical_list: D010455:Peptides; D019275:Radiopharmaceuticals; C000606133:peptide p5 plus 14; D013667:Technetium
keywords: AA amyloid; Molecular imaging radiotracer; Peptide p5 + 14; Technetium-99m