Quantitation of 99m Tc-DPD uptake in patients with transthyretin-related cardiac amyloidosis.

Purpose: Transthyretin (ATTR) amyloidosis is a rare but serious infiltrative disease associated with a wide spectrum of morphologic and functional cardiac involvement. Tc-99m-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 Tc-99m-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 Tc-99m-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 Tc-99m-DPD uptake in the heart was significantly greater in patients with grade-3 uptake than in those with grade-2 uptake.Conclusions: Quantitation of Tc-99m-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.