ORIGINAL ARTICLE Usefulness and limitations of 99m Tc-3,3-diphosphono-1, 2-propanodicarboxylic acid scintigraphy in the aetiological diagnosis of amyloidotic cardiomyopathy Claudio Rapezzi & Candida Cristina Quarta & Pier Luigi Guidalotti & Simone Longhi & Cinzia Pettinato & Ornella Leone & Alessandra Ferlini & Fabrizio Salvi & Pamela Gallo & Christian Gagliardi & Angelo Branzi Received: 27 July 2010 / Accepted: 4 October 2010 / Published online: 11 November 2010 # Springer-Verlag 2010 Abstract Purpose We previously reported in a small series of patients that 99m Tc-3,3-diphosphono-1,2-propanodicarbox- ylic acid ( 99m Tc-DPD) scintigraphy tested positive in transthyretin-related (TTR) (both mutant and wild-type) but not in primary (AL) amyloidotic cardiomyopathy (AC). We extended our study to a larger cohort of patients with AC. Methods We evaluated (1) 45 patients with TTR-related AC (28 mutant and 17 wild-type), (2) 34 with AL-related AC and (3) 15 non-affected controls. Myocardial uptake of 99m Tc-DPD (740 MBq i.v.) was semiquantitatively and visually assessed at 5 min and at 3 h. Results Heart retention (HR) and heart to whole-body retention ratio (H/WB) of late 99m Tc-DPD uptake were higher among TTR-related AC (HR 7.8%; H/WB 10.4) compared with both unaffected controls (HR 3.5%; H/WB 5.7; p < 0.0001) and AL-related AC (HR 4.0%; H/WB 6.1; p < 0.0001). For the diagnosis of TTR-related AC, positive and negative predictive accuracy of visual scoring of cardiac retention were: 80 and 100% (visual score ≥1); 88 and 100% (visual score ≥2); and 100 and 68% (visual score = 3). At adjusted linear regression analysis, TTR aetiology turned out to be the only positive predictor of increasing 99m Tc-DPD uptake in terms of both HR [β 2.5, 95% confidence interval (CI) 1.5–3.5; p <0.0001] and H/WB (β 3.5, 95% CI 2.1–4.9; p <0.0001). Conclusion While 99m Tc-DPD scintigraphy was confirmed to be useful for differentiating TTR from AL-related AC, diagnostic accuracy was lower than previously reported due to a mild degree of tracer uptake in about one third of AL patients. 99m Tc-DPD scintigraphy can provide an accurate differential diagnosis in cases of absent or intense uptake evaluated by visual score. Keywords Amyloid . Cardiomyopathy . 99m Tc-DPD scintigraphy . Differential diagnosis . Accuracy Introduction Amyloidosis is characterized by extracellular accumulation of fibrillary proteins, leading to infiltration and functional impairment of many tissues and organs, including the heart C. Rapezzi (*) : C. C. Quarta : S. Longhi : P. Gallo : C. Gagliardi : A. Branzi Institute of Cardiology, University of Bologna and Policlinico S. Orsola-Malpighi Hospital, via Massarenti 9, 40138 Bologna, Italy e-mail: claudio.rapezzi@unibo.it P. L. Guidalotti : C. Pettinato Nuclear Medicine Unit, S. Orsola-Malpighi Hospital, Bologna, Italy O. Leone Department of Pathology, University of Bologna and S. Orsola-Malpighi Hospital, Bologna, Italy A. Ferlini Department of Diagnostic and Experimental Medicine, Section of Medical Genetics, University of Ferrara, Ferrara, Italy F. Salvi Department of Neurology, Ospedale Bellaria, Bologna, Italy Eur J Nucl Med Mol Imaging (2011) 38:470–478 DOI 10.1007/s00259-010-1642-7