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Nuclear Imaging for Cardiac Amyloidosis: Bone Scan, SPECT/CT, and Amyloid-Targeting PET

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Abstract

Cardiac amyloidosis (CA) is a type of systemic amyloidosis, in which abnormal amyloid fibril is deposited in extracellular space of myocardium. Most common subtypes of CA are amyloidosis of immunoglobulin light chain (AL) and amyloidosis of transthyretin (ATTR). With increase in incidence of CA and development of new drugs, the needs of early and accurate diagnosis of CA are increasing. In CA, bone scan and SPECT/CT have long been used for diagnosis. Currently, bone scan is included in almost all practice guidelines as one of key diagnostic examinations for ATTR CA. In some specific scenarios, bone scan can be used as even a substitute for endomyocardial biopsy. Recently, amyloid-targeting PET that is used for Alzheimer dementia has also been attempted as an imaging method for CA. Although the study results are still insufficient, amyloid-targeting has shown promising potential as an imaging method for CA, particularly in AL. Here, imaging method and clinical application and implication of bone scan, SPECT/CT, and amyloid-targeting PET/CT in CA are reviewed.

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References

  1. Maurer MS, Elliott P, Comenzo R, Semigran M, Rapezzi C. Addressing common questions encountered in the diagnosis and management of cardiac amyloidosis. Circulation. 2017;135:1357–77.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Wechalekar AD, Gillmore JD, Hawkins PN. Systemic amyloidosis. Lancet. 2016;387:2641–54.

    Article  CAS  PubMed  Google Scholar 

  3. Kyle RA, Larson DR, Kurtin PJ, Kumar S, Cerhan JR, Therneau TM, et al. Incidence of AL amyloidosis in Olmsted County, Minnesota, 1990 through 2015. Mayo Clin Proc. 2019;94:465–71.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Muchtar E, Gertz MA, Kumar SK, Lacy MQ, Dingli D, Buadi FK, et al. Improved outcomes for newly diagnosed AL amyloidosis between 2000 and 2014: cracking the glass ceiling of early death. Blood. 2017;129:2111–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. González-López E, Gallego-Delgado M, Guzzo-Merello G, de Haro-Del Moral FJ, Cobo-Marcos M, Robles C, et al. Wild-type transthyretin amyloidosis as a cause of heart failure with preserved ejection fraction. Eur Heart J. 2015;36:2585–94.

    Article  PubMed  Google Scholar 

  6. Martinez-Naharro A, Baksi AJ, Hawkins PN, Fontana M. Diagnostic imaging of cardiac amyloidosis. Nat Rev Cardiol. 2020;17:413–26.

    Article  PubMed  Google Scholar 

  7. Mohammed SF, Mirzoyev SA, Edwards WD, Dogan A, Grogan DR, Dunlay SM, et al. Left ventricular amyloid deposition in patients with heart failure and preserved ejection fraction. JACC Heart Fail. 2014;2:113–22.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Lane T, Fontana M, Martinez-Naharro A, Quarta CC, Whelan CJ, Petrie A, et al. Natural history, quality of life, and outcome in cardiac transthyretin amyloidosis. Circulation. 2019;140:16–26.

    Article  CAS  PubMed  Google Scholar 

  9. Martinez-Naharro A, Hawkins PN, Fontana M. Cardiac amyloidosis. Clin Med (Lond). 2018;18:s30–s5.

    Article  Google Scholar 

  10. Kittleson MM, Maurer MS, Ambardekar AV, Bullock-Palmer RP, Chang PP, Eisen HJ, et al. Cardiac amyloidosis: evolving diagnosis and management: a scientific statement from the American Heart Association. Circulation. 2020;142:e7–e22.

    Article  PubMed  Google Scholar 

  11. Doltra A, Amundsen BH, Gebker R, Fleck E, Kelle S. Emerging concepts for myocardial late gadolinium enhancement MRI. Curr Cardiol Rev. 2013;9:185–90.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Slart R, Glaudemans A, Noordzij W, Bijzet J, Hazenberg BPC, Nienhuis HLA. Time for new imaging and therapeutic approaches in cardiac amyloidosis. Eur J Nucl Med Mol Imaging. 2019;46:1402–6.

    Article  PubMed  Google Scholar 

  13. Hazenberg BP, van Rijswijk MH, Piers DA, Lub-de Hooge MN, Vellenga E, Haagsma EB, et al. Diagnostic performance of 123I-labeled serum amyloid P component scintigraphy in patients with amyloidosis. Am J Med. 2006;119:355.e15–24.

  14. Kula RW, Engel WK, Line BR. Scanning for soft-tissue amyloid. Lancet. 1977;1:92–3.

    Article  CAS  PubMed  Google Scholar 

  15. Chen W, Dilsizian V. Molecular imaging of amyloidosis: will the heart be the next target after the brain? Curr Cardiol Rep. 2012;14:226–33.

    Article  PubMed  Google Scholar 

  16. Pepys MB, Dyck RF, de Beer FC, Skinner M, Cohen AS. Binding of serum amyloid P-component (SAP) by amyloid fibrils. Clin Exp Immunol. 1979;38:284–93.

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Perugini E, Guidalotti PL, Salvi F, Cooke RM, Pettinato C, Riva L, et al. Noninvasive etiologic diagnosis of cardiac amyloidosis using 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid scintigraphy. J Am Coll Cardiol. 2005;46:1076–84.

    Article  PubMed  Google Scholar 

  18. de Haro-del Moral FJ, Sánchez-Lajusticia A, Gómez-Bueno M, García-Pavía P, Salas-Antón C, Segovia-Cubero J. Role of cardiac scintigraphy with 99mTc-DPD in the differentiation of cardiac amyloidosis subtype. Rev Esp Cardiol (Engl Ed). 2012;65:440–6.

  19. Abulizi M, Cottereau AS, Guellich A, Vandeventer S, Galat A, Van Der Gucht A, et al. Early-phase myocardial uptake intensity of (99m)Tc-HMDP vs (99m)Tc-DPD in patients with hereditary transthyretin-related cardiac amyloidosis. J Nucl Cardiol. 2018;25:217–22.

    Article  PubMed  Google Scholar 

  20. Dorbala S, Ando Y, Bokhari S, Dispenzieri A, Falk RH, Ferrari VA, et al. ASNC/AHA/ASE/EANM/HFSA/ISA/SCMR/SNMMI expert consensus recommendations for multimodality imaging in cardiac amyloidosis: part 1 of 2-evidence base and standardized methods of imaging. J Nucl Cardiol. 2019;26:2065–123.

    Article  PubMed  Google Scholar 

  21. Bokhari S, Castaño A, Pozniakoff T, Deslisle S, Latif F, Maurer MS. (99m)Tc-pyrophosphate scintigraphy for differentiating light-chain cardiac amyloidosis from the transthyretin-related familial and senile cardiac amyloidoses. Circ Cardiovasc Imaging. 2013;6:195–201.

  22. Glaudemans AW, van Rheenen RW, van den Berg MP, Noordzij W, Koole M, Blokzijl H, et al. Bone scintigraphy with (99m)technetium-hydroxymethylene diphosphonate allows early diagnosis of cardiac involvement in patients with transthyretin-derived systemic amyloidosis. Amyloid. 2014;21:35–44.

    Article  CAS  PubMed  Google Scholar 

  23. Caobelli F, Braun M, Haaf P, Wild D, Zellweger MJ. Quantitative (99m)Tc-DPD SPECT/CT in patients with suspected ATTR cardiac amyloidosis: feasibility and correlation with visual scores. J Nucl Cardiol. 2019.

  24. Scully PR, Morris E, Patel KP, Treibel TA, Burniston M, Klotz E, et al. DPD quantification in cardiac amyloidosis: a novel imaging biomarker. JACC Cardiovasc Imaging. 2020;13:1353–63.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Malka N, Abulizi M, Kharoubi M, Oghina S, Galat A, Le Bras F, et al. Extracardiac soft tissue uptake, evidenced on early (99m)Tc-HMDP SPECT/CT, helps typing cardiac amyloidosis and demonstrates high prognostic value. Eur J Nucl Med Mol Imaging. 2020;47:2396–406.

    Article  CAS  PubMed  Google Scholar 

  26. Lee J, Kim K, Choi JO, Kim SJ, Jeon ES, Choi JY. 99mTc-DPD scintigraphy and SPECT/CT in patients with AL and ATTR type amyloidosis: potential clinical implications. Medicine (Baltimore). 2020;99:e18905.

  27. Musumeci MB, Cappelli F, Russo D, Tini G, Canepa M, Milandri A, et al. Low sensitivity of bone scintigraphy in detecting Phe64Leu mutation-related transthyretin cardiac amyloidosis. JACC Cardiovasc Imaging. 2020;13:1314–21.

    Article  PubMed  Google Scholar 

  28. Brownrigg J, Lorenzini M, Lumley M, Elliott P. Diagnostic performance of imaging investigations in detecting and differentiating cardiac amyloidosis: a systematic review and meta-analysis. ESC Heart Fail. 2019;6:1041–51.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Di Bella G, Minutoli F, Piaggi P, Casale M, Mazzeo A, Zito C, et al. Quantitative comparison between amyloid deposition detected by (99m)Tc-diphosphonate imaging and myocardial deformation evaluated by strain echocardiography in transthyretin-related cardiac amyloidosis. Circ J. 2016;80:1998–2003.

    Article  PubMed  Google Scholar 

  30. Vranian MN, Sperry BW, Hanna M, Hachamovitch R, Ikram A, Brunken RC, et al. Technetium pyrophosphate uptake in transthyretin cardiac amyloidosis: associations with echocardiographic disease severity and outcomes. J Nucl Cardiol. 2018;25:1247–56.

    Article  PubMed  Google Scholar 

  31. Castano A, Haq M, Narotsky DL, Goldsmith J, Weinberg RL, Morgenstern R, et al. Multicenter study of planar technetium 99m pyrophosphate cardiac imaging: predicting survival for patients with ATTR cardiac amyloidosis. JAMA Cardiol. 2016;1:880–9.

    Article  PubMed  Google Scholar 

  32. Haq M, Pawar S, Berk JL, Miller EJ, Ruberg FL. Can (99m)Tc-pyrophosphate aid in early detection of cardiac involvement in asymptomatic variant TTR amyloidosis? JACC Cardiovasc Imaging. 2017;10:713–4.

    Article  PubMed  Google Scholar 

  33. Minutoli F, Di Bella G, Mazzeo A, Laudicella R, Gentile L, Russo M, et al. Serial scanning with (99m)Tc-3, 3-diphosphono-1, 2-propanodicarboxylic acid ((99m)Tc-DPD) for early detection of cardiac amyloid deposition and prediction of clinical worsening in subjects carrying a transthyretin gene mutation. J Nucl Cardiol. 2019.

  34. Bennani Smires Y, Victor G, Ribes D, Berry M, Cognet T, Méjean S, et al. Pilot study for left ventricular imaging phenotype of patients over 65 years old with heart failure and preserved ejection fraction: the high prevalence of amyloid cardiomyopathy. Int J Cardiovasc Imaging. 2016;32:1403–13.

    Article  PubMed  Google Scholar 

  35. Longhi S, Lorenzini M, Gagliardi C, Milandri A, Marzocchi A, Marrozzini C, et al. Coexistence of degenerative aortic stenosis and wild-type transthyretin-related cardiac amyloidosis. JACC Cardiovasc Imaging. 2016;9:325–7.

    Article  PubMed  Google Scholar 

  36. Castaño A, Narotsky DL, Hamid N, Khalique OK, Morgenstern R, DeLuca A, et al. Unveiling transthyretin cardiac amyloidosis and its predictors among elderly patients with severe aortic stenosis undergoing transcatheter aortic valve replacement. Eur Heart J. 2017;38:2879–87.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Sperry BW, Reyes BA, Ikram A, Donnelly JP, Phelan D, Jaber WA, et al. Tenosynovial and cardiac amyloidosis in patients undergoing carpal tunnel release. J Am Coll Cardiol. 2018;72:2040–50.

    Article  PubMed  Google Scholar 

  38. Longhi S, Guidalotti PL, Quarta CC, Gagliardi C, Milandri A, Lorenzini M, et al. Identification of TTR-related subclinical amyloidosis with 99mTc-DPD scintigraphy. JACC Cardiovasc Imaging. 2014;7:531–2.

    Article  PubMed  Google Scholar 

  39. Mohamed-Salem L, Santos-Mateo JJ, Sanchez-Serna J, Hernández-Vicente Á, Reyes-Marle R, Castellón Sánchez MI, et al. Prevalence of wild type ATTR assessed as myocardial uptake in bone scan in the elderly population. Int J Cardiol. 2018;270:192–6.

    Article  PubMed  Google Scholar 

  40. Kim HM, Sohn DW, Paeng JC. Prevalence of positive (99 m)Tc-DPD scintigraphy as an indicator of the prevalence of wild-type transthyretin amyloidosis in the elderly. Int Heart J. 2019;60:643–7.

    Article  CAS  PubMed  Google Scholar 

  41. Singh V, Falk R, Di Carli MF, Kijewski M, Rapezzi C, Dorbala S. State-of-the-art radionuclide imaging in cardiac transthyretin amyloidosis. J Nucl Cardiol. 2019;26:158–73.

    Article  PubMed  Google Scholar 

  42. Gillmore JD, Maurer MS, Falk RH, Merlini G, Damy T, Dispenzieri A, et al. Nonbiopsy diagnosis of cardiac transthyretin amyloidosis. Circulation. 2016;133:2404–12.

    Article  CAS  PubMed  Google Scholar 

  43. Maurer MS, Bokhari S, Damy T, Dorbala S, Drachman BM, Fontana M, et al. Expert consensus recommendations for the suspicion and diagnosis of transthyretin cardiac amyloidosis. Circ Heart Fail. 2019;12:e006075.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Hanna M, Ruberg FL, Maurer MS, Dispenzieri A, Dorbala S, Falk RH, et al. Cardiac scintigraphy with technetium-99m-labeled bone-seeking tracers for suspected amyloidosis: JACC Review Topic of the Week. J Am Coll Cardiol. 2020;75:2851–62.

    Article  CAS  PubMed  Google Scholar 

  45. Antoni G, Lubberink M, Estrada S, Axelsson J, Carlson K, Lindsjö L, et al. In vivo visualization of amyloid deposits in the heart with 11C-PIB and PET. J Nucl Med. 2013;54:213–20.

    Article  CAS  PubMed  Google Scholar 

  46. Dorbala S, Vangala D, Semer J, Strader C, Bruyere JR Jr, Di Carli MF, et al. Imaging cardiac amyloidosis: a pilot study using 18F-florbetapir positron emission tomography. Eur J Nucl Med Mol Imaging. 2014;41:1652–62.

    Article  CAS  PubMed  Google Scholar 

  47. Park MA, Padera RF, Belanger A, Dubey S, Hwang DH, Veeranna V, et al. 18F-Florbetapir binds specifically to myocardial light chain and transthyretin amyloid deposits: autoradiography study. Circ Cardiovasc Imaging. 2015;8.

  48. Law WP, Wang WY, Moore PT, Mollee PN, Ng AC. Cardiac amyloid imaging with 18F-florbetaben PET: a pilot study. J Nucl Med. 2016;57:1733–9.

    Article  CAS  PubMed  Google Scholar 

  49. Lhommel R, Sempoux C, Ivanoiu A, Michaux L, Gerber B. Is 18F-flutemetamol PET/CT able to reveal cardiac amyloidosis? Clin Nucl Med. 2014;39:747–9.

    Article  PubMed  Google Scholar 

  50. Lee SP, Lee ES, Choi H, Im HJ, Koh Y, Lee MH, et al. 11C-Pittsburgh B PET imaging in cardiac amyloidosis. JACC Cardiovasc Imaging. 2015;8:50–9.

    Article  PubMed  Google Scholar 

  51. Kim YJ, Ha S, Kim YI. Cardiac amyloidosis imaging with amyloid positron emission tomography: a systematic review and meta-analysis. J Nucl Cardiol. 2020;27:123–32.

    Article  PubMed  Google Scholar 

  52. Lee SP, Suh HY, Park S, Oh S, Kwak SG, Kim HM, et al. Pittsburgh B compound positron emission tomography in patients with AL cardiac amyloidosis. J Am Coll Cardiol. 2020;75:380–90.

    Article  CAS  PubMed  Google Scholar 

  53. Maurer MS, Schwartz JH, Gundapaneni B, Elliott PM, Merlini G, Waddington-Cruz M, et al. Tafamidis treatment for patients with transthyretin amyloid cardiomyopathy. N Engl J Med. 2018;379:1007–16.

    Article  CAS  PubMed  Google Scholar 

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Funding

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (Ministry of Science and ICT) (No. NRF-2020M2D9A104072).

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Authors and Affiliations

  1. Department of Nuclear Medicine, Seoul National University Hospital, Seoul, Republic of Korea

    Jin Chul Paeng

  2. Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, 06351, Seoul, Republic of Korea

    Joon Young Choi

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  1. Jin Chul Paeng
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Correspondence to Joon Young Choi.

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Conflict of Interest

Jin Chul Paeng, and Joon Young Choi declare that they received consulting fees from Pfizer Ltd. in the Republic of Korea regarding bone scintigraphy in amyloidosis within the past 12 months. However, the company did not involve the preparation of this manuscript.

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This study procedure followed the medical research protocols and ethics guidelines defined by the World Medical Association’s Declaration of Helsinki throughout the study.

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Informed consent was not necessary, because the study design was a review based on previous studies.

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Paeng, J.C., Choi, J.Y. Nuclear Imaging for Cardiac Amyloidosis: Bone Scan, SPECT/CT, and Amyloid-Targeting PET. Nucl Med Mol Imaging 55, 61–70 (2021). https://doi.org/10.1007/s13139-020-00681-4

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  • DOI: https://doi.org/10.1007/s13139-020-00681-4

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