Dynamic PET and SPECT imaging with radioiodinated, amyloid-reactive peptide p5 in mice

A positive role for peptide dehalogenation

Emily Martin, Stephen Kennel, Tina Richey, Craig Wooliver, Dustin Osborne, Angela Williams, Alan Stuckey, Jonathan Wall

Research output: Contribution to journalArticle

11 Citations (Scopus)

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 72 h 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.

Original languageEnglish (US)
Pages (from-to)63-70
Number of pages8
JournalPeptides
Volume60
DOIs
StatePublished - Jan 1 2014
Externally publishedYes

Fingerprint

Dehalogenation
Single-Photon Emission-Computed Tomography
Amyloid
Imaging techniques
Peptides
Amyloidosis
Molecular imaging
Molecular Imaging
Iodine
Deposits
Proteostasis Deficiencies
Kinetics
Amyloid Plaques
Proteoglycans
Proteins
Blood
Tissue
Injections
Antibodies
Monitoring

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Physiology
  • Endocrinology
  • Cellular and Molecular Neuroscience

Cite this

Dynamic PET and SPECT imaging with radioiodinated, amyloid-reactive peptide p5 in mice : A positive role for peptide dehalogenation. / Martin, Emily; Kennel, Stephen; Richey, Tina; Wooliver, Craig; Osborne, Dustin; Williams, Angela; Stuckey, Alan; Wall, Jonathan.

In: Peptides, Vol. 60, 01.01.2014, p. 63-70.

Research output: Contribution to journalArticle

@article{07b7e008891c4a31adaafa55402a19c2,
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 72 h 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.",
author = "Emily Martin and Stephen Kennel and Tina Richey and Craig Wooliver and Dustin Osborne and Angela Williams and Alan Stuckey and Jonathan Wall",
year = "2014",
month = "1",
day = "1",
doi = "10.1016/j.peptides.2014.07.024",
language = "English (US)",
volume = "60",
pages = "63--70",
journal = "Peptides",
issn = "0196-9781",
publisher = "Elsevier Inc.",

}

TY - JOUR

T1 - Dynamic PET and SPECT imaging with radioiodinated, amyloid-reactive peptide p5 in mice

T2 - A positive role for peptide dehalogenation

AU - Martin, Emily

AU - Kennel, Stephen

AU - Richey, Tina

AU - Wooliver, Craig

AU - Osborne, Dustin

AU - Williams, Angela

AU - Stuckey, Alan

AU - Wall, Jonathan

PY - 2014/1/1

Y1 - 2014/1/1

N2 - 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 72 h 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.

AB - 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 72 h 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.

UR - http://www.scopus.com/inward/record.url?scp=84906513548&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84906513548&partnerID=8YFLogxK

U2 - 10.1016/j.peptides.2014.07.024

DO - 10.1016/j.peptides.2014.07.024

M3 - Article

VL - 60

SP - 63

EP - 70

JO - Peptides

JF - Peptides

SN - 0196-9781

ER -