Quantitation of ^99mTc-DPD uptake in patients with transthyretin-related cardiac amyloidosis

Abstract

Purpose: Transthyretin (ATTR) amyloidosis is a rare but serious infiltrative disease associated with a wide spectrum of morphologic and functional cardiac involvement. ^99mTc-labelled 3,3-diphosphono-1,2-propanodicarboxylic acid (DPD), initially developed as a bone-seeking radiotracer, is remarkably sensitive for imaging cardiac ATTR amyloid deposits. Our aim was to investigate the feasibility and utility of estimating ^99mTc-DPD uptake in myocardial tissue; this has the potential to yield reliable quantitative information on cardiac amyloid burden, which is urgently required to monitor disease progression and response to novel treatments.

Methods: Three methods of quantitation were developed and tested on 74 patients with proven cardiac ATTR amyloidosis who had recently undergone ^99mTc-DPD planar whole-body imaging and SPECT-CT. Quantitative results were compared to measurements of extracellular volume fraction (ECV) by cardiac magnetic resonance imaging, a validated technique for measuring amyloid burden.

Results: An experienced clinician graded uptake using a widely-used visual scoring system as 1 (n = 15), 2 (n = 39) or 3 (n = 20). Linear correlations between the SPECT and ECV data (p < .001) were demonstrated. None of the methods showed that ^99mTc-DPD uptake in the heart was significantly greater in patients with grade-3 uptake than in those with grade-2 uptake.

Conclusions: Quantitation of ^99mTc-DPD uptake in cardiac transthyretin amyloid deposits is complex and is hindered by competition for radiotracer with amyloid in skeletal muscle. The latter underlies differences in uptake between grade-2 and grade-3 patients, not cardiac uptake.

KEYWORDS:

• amyloidosis
• ATTR
• cardiology
• DPD
• quantitation
• SPECT

Acknowledgements

JCR, DFH, MB, and JP were responsible for data collection and analysis; JAS for development of the in-house OsiriX plugin used; and JDG, ADW, PNH, and MF for interpretation of results and critical review of the manuscript.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

GE Healthcare provided a trial licence for the use of Q.Metrix.