James C Ross1,2, David F Hutt1, Maria Burniston1,3, Joanne Page1,4, Jennifer A Steeden5, Julian D Gillmore1, Ashutosh D Wechalekar1, Philip N Hawkins1, Marianna Fontana1. 1. a National Amyloidosis Centre , UCL Medical School (Royal Free Campus) , London , UK. 2. b Institute of Nuclear Medicine , University College London Hospitals NHS Foundation Trust , London , UK. 3. c Nuclear Medicine Department, Nuclear Medicine , Barts Health NHS Trust , London , UK. 4. d Nuclear Medicine Department , Royal Free London NHS Foundation Trust , London , UK. 5. e UCL Centre for Cardiovascular Imaging , University College London , London , UK.
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.
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 ATTRamyloidosis 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.
Authors: Maria Papathanasiou; Christoph Rischpler; Lukas Kessler; Pedro Fragoso Costa; David Kersting; Walter Jentzen; Manuel Weber; Peter Lüdike; Alexander Carpinteiro; Sara Oubari; Tim Hagenacker; Andreas Thimm; Tienush Rassaf; Ken Herrmann Journal: J Nucl Cardiol Date: 2022-05-13 Impact factor: 5.952
Authors: Jean Michel Saad; Ahmed Ibrahim Ahmed; Yushui Han; Subha Saeed; Payam Pournazari; Mouaz H Al-Mallah Journal: Heart Fail Rev Date: 2021-10-28 Impact factor: 4.654
Authors: Viktor Löfbacka; Jan Axelsson; Björn Pilebro; Ole B Suhr; Per Lindqvist; Torbjörn Sundström Journal: Eur J Nucl Med Mol Imaging Date: 2020-12-26 Impact factor: 9.236
Authors: A Yilmaz; J Bauersachs; F Bengel; R Büchel; I Kindermann; K Klingel; F Knebel; B Meder; C Morbach; E Nagel; E Schulze-Bahr; F Aus dem Siepen; N Frey Journal: Clin Res Cardiol Date: 2021-01-18 Impact factor: 5.460
Authors: Sharmila Dorbala; Mi-Ae Park; Sarah Cuddy; Vasvi Singh; Kyle Sullivan; Sirwoo Kim; Rodney H Falk; Viviany R Taqueti; Hicham Skali; Ron Blankstein; Camden Bay; Marie F Kijewski; Marcelo F Di Carli Journal: J Nucl Med Date: 2020-09-04 Impact factor: 11.082