A Binding-Site Barrier Affects Imaging Efficiency of High Affinity Amyloid-Reactive Peptide Radiotracers In Vivo

Jonathan Wall, Angela Williams, Tina Richey, Alan Stuckey, Ying Huang, Craig Wooliver, Sallie Macy, Robert Heidel, Neil Gupta, Angela Lee, Brianna Rader, Emily Martin, Stephen Kennel

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Amyloid is a complex pathology associated with a growing number of diseases including Alzheimer's disease, type 2 diabetes, rheumatoid arthritis, and myeloma. The distribution and extent of amyloid deposition in body organs establishes the prognosis and can define treatment options; therefore, determining the amyloid load by using non-invasive molecular imaging is clinically important. We have identified a heparin-binding peptide designated p5 that, when radioiodinated, was capable of selectively imaging systemic visceral AA amyloidosis in a murine model of the disease. The p5 peptide was posited to bind effectively to amyloid deposits, relative to similarly charged polybasic heparin-reactive peptides, because it adopted a polar α helix secondary structure. We have now synthesized a variant, p5R, in which the 8 lysine amino acids of p5 have been replaced with arginine residues predisposing the peptide toward the α helical conformation in an effort to enhance the reactivity of the peptide with the amyloid substrate. The p5R peptide had higher affinity for amyloid and visualized AA amyloid in mice by using SPECT/CT imaging; however, the microdistribution, as evidenced in micro-autoradiographs, was dramatically altered relative to the p5 peptide due to its increased affinity and a resultant "binding site barrier" effect. These data suggest that radioiodinated peptide p5R may be optimal for the in vivo detection of discreet, perivascular amyloid, as found in the brain and pancreatic vasculature, by using molecular imaging techniques; however, peptide p5, due to its increased penetration, may yield more quantitative imaging of expansive tissue amyloid deposits.

Original languageEnglish (US)
Article numbere66181
JournalPloS one
Volume8
Issue number6
DOIs
StatePublished - Jun 4 2013

Fingerprint

amyloid
Amyloid
binding sites
Binding Sites
image analysis
peptides
Imaging techniques
Peptides
Molecular imaging
Molecular Imaging
Amyloid Plaques
heparin
Heparin
Deposits
amyloidosis
myeloma
rheumatoid arthritis
autoradiography
Pathology
Amyloidosis

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

A Binding-Site Barrier Affects Imaging Efficiency of High Affinity Amyloid-Reactive Peptide Radiotracers In Vivo. / Wall, Jonathan; Williams, Angela; Richey, Tina; Stuckey, Alan; Huang, Ying; Wooliver, Craig; Macy, Sallie; Heidel, Robert; Gupta, Neil; Lee, Angela; Rader, Brianna; Martin, Emily; Kennel, Stephen.

In: PloS one, Vol. 8, No. 6, e66181, 04.06.2013.

Research output: Contribution to journalArticle

Wall, Jonathan ; Williams, Angela ; Richey, Tina ; Stuckey, Alan ; Huang, Ying ; Wooliver, Craig ; Macy, Sallie ; Heidel, Robert ; Gupta, Neil ; Lee, Angela ; Rader, Brianna ; Martin, Emily ; Kennel, Stephen. / A Binding-Site Barrier Affects Imaging Efficiency of High Affinity Amyloid-Reactive Peptide Radiotracers In Vivo. In: PloS one. 2013 ; Vol. 8, No. 6.
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