Tc-99m Radiolabeled Peptide P5 + 14 is an Effective Probe for SPECT Imaging of Systemic Amyloidosis

Overview

Journal Mol Imaging Biol

Publisher Springer

Specialties Molecular Biology
Radiology

Date 2015 Nov 18

PMID 26573301

Citations 8

Authors

Stephen J Kennel

Alan Stuckey

Helen P McWilliams-Koeppen

Tina Richey

Jonathan S Wall

Affiliations

Soon will be listed here.

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 [(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.

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: [(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.

Citing Articles

2025 Update Consensus of Tc-Pyrophosphate Scintigraphy in the Transthyretin Cardiac Amyloidosis from the Taiwan Society of Cardiology and the Society of Nuclear Medicine of the Republic of China.

Wang S, Huang Y, Chen Y, Tsai C, Ko C, Lin Y Acta Cardiol Sin. 2025; 41(1):55-71.

PMID: 39776923 PMC: 11701493. DOI: 10.6515/ACS.202501_41(1).20241027A.

Preclinical evaluation of Tc-99m p5+14 peptide for SPECT detection of cardiac amyloidosis.

Kennel S, Jackson J, Stuckey A, Richey T, Foster J, Wall J PLoS One. 2024; 19(4):e0301756.

PMID: 38578730 PMC: 10997057. DOI: 10.1371/journal.pone.0301756.

Development and characterization of a prototypic pan-amyloid clearing agent - a novel murine peptide-immunoglobulin fusion.

Foster J, Balachandran M, Hancock T, Martin E, Macy S, Wooliver C Front Immunol. 2023; 14:1275372.

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Cardiac Amyloid Quantification Using I-Evuzamitide (I-P5+14) Versus F-Florbetapir: A Pilot PET/CT Study.

Clerc O, Cuddy S, Robertson M, Vijayakumar S, Canseco Neri J, Chemburkar V JACC Cardiovasc Imaging. 2023; 16(11):1419-1432.

PMID: 37676210 PMC: 10758980. DOI: 10.1016/j.jcmg.2023.07.007.

Clinical Confirmation of Pan-Amyloid Reactivity of Radioiodinated Peptide I-p5+14 (AT-01) in Patients with Diverse Types of Systemic Amyloidosis Demonstrated by PET/CT Imaging.

Martin E, Stuckey A, Powell D, Lands R, Whittle B, Wooliver C Pharmaceuticals (Basel). 2023; 16(4).

PMID: 37111386 PMC: 10144944. DOI: 10.3390/ph16040629.

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