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Tc-99m Radiolabeled Peptide p5 + 14 is an Effective Probe for SPECT Imaging of Systemic Amyloidosis

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Abstract

Purpose

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.

Procedures

Radiochemical yield, purity, and biological activity of [99mTc]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 [99mTc]p5 + 14 in hepatosplenic amyloid was evaluated using region of interest (ROI) and tissue counting measurements.

Results

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.

Conclusion

[99mTc]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.

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Fig. 1
Fig. 2

Abbreviations

AA:

Serum amyloid protein A

SPECT/CT:

Single-photon emission computed/X-ray computed tomography

ARG:

Microautoradiography

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Acknowledgments

This work was supported by PHS grant R01DK079984 from The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), as well as funds from the Molecular Imaging and Translational Research Program, and Department of Medicine at UTMCK. We thank Dr. Emily Martin for help in proofreading and annotating this article.

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Authors and Affiliations

  1. Department of Medicine, University of Tennessee, Graduate School of Medicine, Knoxville, TN, USA

    Stephen J. Kennel, Helen P. McWilliams-Koeppen, Tina Richey & Jonathan S. Wall

  2. Department of Radiology, University of Tennessee, Graduate School of Medicine, Knoxville, TN, USA

    Stephen J. Kennel, Alan Stuckey & Jonathan S. Wall

  3. University of Tennessee Medical Center, 1924 Alcoa Highway, Knoxville, TN, 37920, USA

    Stephen J. Kennel

Authors
  1. Stephen J. Kennel
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  2. Alan Stuckey
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  3. Helen P. McWilliams-Koeppen
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  4. Tina Richey
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  5. Jonathan S. Wall
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Corresponding author

Correspondence to Stephen J. Kennel.

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Ethical Statement

All animal studies were performed in accordance with protocols approved by the University of Tennessee Institutional Animal Care and Use Committee and in accordance with the guidelines provided by Office of Laboratory Animal Welfare (OLAW) and the Guide for the Care and Use of Laboratory Animals. The University of Tennessee Graduate School of Medicine is a AAALAC-I-accredited institution.

Conflict of Interest

JSW and SJK are inventors on a US patent (# 8.808 666) that describes the use of peptide p5 as an imaging agent for amyloidosis. JSW, SJK, TR, and AS are owners of Solex LLC, which sub-licensed rights to intellectual property from the University of Tennessee.

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Kennel, S.J., Stuckey, A., McWilliams-Koeppen, H.P. et al. Tc-99m Radiolabeled Peptide p5 + 14 is an Effective Probe for SPECT Imaging of Systemic Amyloidosis. Mol Imaging Biol 18, 483–489 (2016). https://doi.org/10.1007/s11307-015-0914-9

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  • DOI: https://doi.org/10.1007/s11307-015-0914-9

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