Skip to main content

Advertisement

SpringerLink
Log in

Molecular Imaging of Amyloidosis: Will the Heart Be the Next Target After the Brain?

  • Nuclear Cardiology (V Dilsizian, Section Editor)
  • Published:
Current Cardiology Reports Aims and scope Submit manuscript

Abstract

Amyloidosis is a heterogeneous group of diseases with a common feature of extracellular deposition and infiltration of different types of amyloid fibrils in various organs. For example, Alzheimer’s disease is characterized by deposition of amyloid β in the brain. Radiolabeled positron emission tomography (PET) tracers, mainly derivatives of thioflavin-T, were recently introduced for identification of amyloid β plaques in Alzheimer’s patients. Such advances of amyloid β plaque imaging of the brain may shed light into imaging of other organs in amyloidosis patients, such as the heart. Cardiac infiltration of amyloid confers poor clinical outcomes, which renders early diagnosis for appropriate clinical management. At present, nuclear imaging of cardiac amyloidosis is predominantly accomplished with bone-seeking radiotracers, such as 99m-technetium-labeled pyrophosphate (99mTc-PYP), 99m-technetium-methylene diphosphonate (99mTc-MDP), and 99m-technetium-3,3,-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD), with conflicting results in terms of diagnostic performance, with the exception for 99mTc-DPD, which may differentiate light-chain amyloidosis from transthyretin-related cardiac amyloidosis. Although other non–bone-seeking radiotracers such as iodine-123-labeled amyloid P component (123I-SAP), 123-iodine-Meta-iodobenzylguanidine (123I-mIBG), 99m-technetium-labeled protease inhibitor, and indium-111-labeled amyloid antibodies have also shown some success in identifying cardiac amyloidosis, the future, however, may lie in labeling derivatives of thioflavin-T. With the recent success of visualizing deposition of amyloid β in the brain, the US Food and Drug Administration–approved PET imaging agent 18F-florbetapir may be used to target cardiac amyloidosis next.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. Sipe JD, Benson MD, Buxbaum JN, et al. Amyloid fibril protein nomenclature: 2010 recommendations from the nomenclature committee of the International Society of Amyloidosis. Amyloid. 2010;17:101–4.

    Article  PubMed  CAS  Google Scholar 

  2. Kyle RA, Gertz MA. Primary systemic amyloidosis: clinical and laboratory features in 474 cases. Semin Hematol. 1995;32:45–59.

    PubMed  CAS  Google Scholar 

  3. Cornwell GG, Murdoch WL, Kyle RA, et al. Frequency and distribution of senile cardiovascular amyloid. A clinicopathologic correlation. Am J Med. 1983;75:618–23.

    Article  PubMed  Google Scholar 

  4. Jacobson DR, Pastore RD, Yaghoubian R, et al. Variant-sequence transthyretin (isoleucine 122) in late-onset cardiac amyloidosis in black Americans. N Engl J Med. 1997;336:466–73.

    Article  PubMed  CAS  Google Scholar 

  5. Desai HV, Aronow WS, Peterson SJ, et al. Cardiac amyloidosis: approaches to diagnosis and management. Cardiol Rev. 2010;18:1–11.

    Article  PubMed  Google Scholar 

  6. Dubrey SW, Cha K, Simms RW, et al. Electrocardiography and Doppler echocardiography in secondary (AA) amyloidosis. Am J Cardiol. 1996;77:313–5.

    Article  PubMed  CAS  Google Scholar 

  7. Biancalana M, Koide S. Molecular mechanism of Thioflavin-T binding to amyloid fibrils. Biochim Biophys Acta. 2010;1804:1405–12.

    PubMed  CAS  Google Scholar 

  8. Serdons K, Verduyckt T, Vanderghinste D, et al. Synthesis of 18F-labelled 2-(4′-fluorophenyl)-1,3-benzothiazole and evaluation as amyloid imaging agent in comparison with [11C]PIB. Bioorg Med Chem Lett. 2009;19:602–5.

    Article  PubMed  CAS  Google Scholar 

  9. Klunk WE, Engler H, Nordberg A, et al. Imaging brain amyloid in Alzheimer's disease with Pittsburgh Compound-B. Ann Neurol. 2004;55:306–19.

    Article  PubMed  CAS  Google Scholar 

  10. Svedberg MM, Hall H, Hellstrom-Lindahl E, et al. [(11)C]PIB-amyloid binding and levels of Abeta40 and Abeta42 in postmortem brain tissue from Alzheimer patients. Neurochem Int. 2009;54:347–57.

    Article  PubMed  CAS  Google Scholar 

  11. Lin KJ, Hsu WC, Hsiao IT, et al. Whole-body biodistribution and brain PET imaging with [18F]AV-45, a novel amyloid imaging agent–a pilot study. Nucl Med Biol. 2010;37:497–508.

    Article  PubMed  CAS  Google Scholar 

  12. Wong DF, Rosenberg PB, Zhou Y, et al. In vivo imaging of amyloid deposition in Alzheimer disease using the radioligand 18F-AV-45 (florbetapir [corrected] F18). J Nucl Med. 2010;51:913–20. This was an open-label, multicenter brain imaging, metabolism, and safety study of 18F -florbetapir-PET imaging on 16 patients with Alzheimer’s disease (AD) and 16 cognitively healthy controls. The cortical-to-cerebellar standardized uptake value ratios (SUVRs) in AD patients showed continual substantial increases through 30 min after tracer administration, reaching a plateau within 50 min. The cortical average SUVR was significantly higher in AD than controls. The results indicated that 18F -florbetapir was well tolerated, and PET imaging showed significant discrimination between AD and controls.

    Article  PubMed  CAS  Google Scholar 

  13. Clark CM, Schneider JA, Bedell BJ, et al. Use of florbetapir-PET for imaging beta-amyloid pathology. JAMA. 2011;305:275–83. The study prospectively evaluated brain florbetapir-PET imaging in patients from hospice, long-term care facilities near the end of their lives and compared with immunohistochemistry and silver stain measures of brain β-amyloid after their death. Both visual interpretation of the florbetapir-PET images and mean quantitative estimations of cortical uptake were correlated well with presence and quantity of β-amyloid pathology at autopsy as measured by immunohistochemistry and silver stain neuritic plaque score. Florbetapir-PET scans were negative in healthy controls.

    Article  PubMed  CAS  Google Scholar 

  14. Wizenberg TA, Muz J, Sohn YH, et al. Value of positive myocardial technetium-99m-pyrophosphate scintigraphy in the noninvasive diagnosis of cardiac amyloidosis. Am Heart J. 1982;103:468–73.

    Article  PubMed  CAS  Google Scholar 

  15. Falk RH, Lee VW, Rubinow A, et al. Sensitivity of technetium-99m-pyrophosphate scintigraphy in diagnosing cardiac amyloidosis. Am J Cardiol. 1983;51:826–30.

    Article  PubMed  CAS  Google Scholar 

  16. Gertz MA, Brown ML, Hauser MF, et al. Utility of technetium Tc 99m pyrophosphate bone scanning in cardiac amyloidosis. Arch Intern Med. 1987;147:1039–44.

    Article  PubMed  CAS  Google Scholar 

  17. Eriksson P, Backman C, Bjerle P, et al. Non-invasive assessment of the presence and severity of cardiac amyloidosis. A study in familial amyloidosis with polyneuropathy by cross sectional echocardiography and technetium-99m pyrophosphate scintigraphy. Br Heart J. 1984;52:321–6.

    Article  PubMed  CAS  Google Scholar 

  18. Hongo M, Yamada H, Okubo S, et al. Cardiac involvement in systemic amyloidosis: myocardial scintigraphic evaluation. J Cardiogr. 1985;15:163–80.

    PubMed  CAS  Google Scholar 

  19. Ak I, Vardareli E, Erdinĉ O, et al. Myocardial Tc-99m MDP uptake on a bone scan in senile systemic amyloidosis with cardiac involvement. Clin Nucl Med. 2000;25:826–7.

    Article  PubMed  CAS  Google Scholar 

  20. Lee VW, Caldarone AG, Falk RH, et al. Amyloidosis of heart and liver: comparison of Tc-99m pyrophosphate and Tc-99m methylene diphosphonate for detection. Radiology. 1983;148:239–42.

    PubMed  CAS  Google Scholar 

  21. Perugini E, Guidalotti PL, Salvi F, 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 

  22. Rapezzi C, Quarta CC, Guidalotti PL, et al. Usefulness and limitations of 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid scintigraphy in the aetiological diagnosis of amyloidotic cardiomyopathy. Eur J Nucl Med Mol Imaging. 2011;38:470–8. This was a clinical study with the largest cohort of amyloidosis patients in the literature to date (45 patients with ATTR, 34 with AL, and 15 controls) to evaluate the role of 99m Tc-DPD scintigraphy in differentiation of TTR from AL-related cardiac amyloidosis. The results showed that although 99m Tc-DPD was confirmed to be useful for differentiating TTR from AL-related cardiac amyloidosis, the diagnostic accuracy was lower than previously reported in a smaller group of patients (100% sensitivity and accuracy) due to a mild degree tracer uptake in about one third of AL patients. However, 99m Tc-DPD scan can provide an accurate differential diagnosis in cases of absent or intense uptake.

    Article  PubMed  Google Scholar 

  23. Hawkins PN. Serum amyloid P component scintigraphy for diagnosis and monitoring amyloidosis. Curr Opin Nephrol Hypertens. 2002;11:649–55.

    Article  PubMed  Google Scholar 

  24. Hawkins PN, Lavender JP, Pepys MB. Evaluation of systemic amyloidosis by scintigraphy with 123I-labeled serum amyloid P component. N Engl J Med. 1990;323:508–13.

    Article  PubMed  CAS  Google Scholar 

  25. Hazenberg BP, van Rijswijk MH, Lub-de Hooge MN, et al. Diagnostic performance and prognostic value of extravascular retention of 123I-labeled serum amyloid P component in systemic amyloidosis. J Nucl Med. 2007;48:865–72.

    Article  PubMed  CAS  Google Scholar 

  26. Sojan SM, Smyth DR, Tsopelas C, et al. Pharmacokinetics and normal scintigraphic appearance of 99mTc aprotinin. Nucl Med Commun. 2005;26:535–9.

    Article  PubMed  CAS  Google Scholar 

  27. Aprile C, Marinone G, Saponaro R, et al. Cardiac and pleuropulmonary AL amyloid imaging with technetium-99m labelled aprotinin. Eur J Nucl Med. 1995;22:1393–401.

    Article  PubMed  CAS  Google Scholar 

  28. Schaadt BK, Hendel HW, Gimsing P, et al. 99mTc-aprotinin scintigraphy in amyloidosis. J Nucl Med. 2003;44:177–83.

    PubMed  Google Scholar 

  29. Han S, Chong V, Murray T, et al. Preliminary experience of 99mTc-Aprotinin scintigraphy in amyloidosis. Eur J Haematol. 2007;79:494–500.

    Article  PubMed  Google Scholar 

  30. Chen W, Cao Q, Dilsizian V. Variation of heart-to-mediastinal ratio in (123)I-mIBG cardiac sympathetic imaging: its affecting factors and potential corrections. Curr Cardiol Rep. 2011;13:132–7.

    Article  PubMed  Google Scholar 

  31. Nakata T, Shimamoto K, Yonekura S, et al. Cardiac sympathetic denervation in transthyretin-related familial amyloidotic polyneuropathy: detection with iodine-123-MIBG. J Nucl Med. 1995;36:1040–2.

    PubMed  CAS  Google Scholar 

  32. Tanaka M, Hongo M, Kinoshita O, et al. Iodine-123 metaiodobenzylguanidine scintigraphic assessment of myocardial sympathetic innervation in patients with familial amyloid polyneuropathy. J Am Coll Cardiol. 1997;29:168–74.

    Article  PubMed  CAS  Google Scholar 

  33. Hongo M, Urushibata K, Kai R, et al. Iodine-123 metaiodobenzylguanidine scintigraphic analysis of myocardial sympathetic innervation in patients with AL (primary) amyloidosis. Am Heart J. 2002;144:122–9.

    Article  PubMed  CAS  Google Scholar 

  34. Delahaye N, Dinanian S, Slama MS, et al. Cardiac sympathetic denervation in familial amyloid polyneuropathy assessed by iodine-123 metaiodobenzylguanidine scintigraphy and heart rate variability. Eur J Nucl Med. 1999;26:416–24.

    Article  PubMed  CAS  Google Scholar 

  35. Solomon A, Weiss DT, Wall JS. Immunotherapy in systemic primary (AL) amyloidosis using amyloid-reactive monoclonal antibodies. Cancer Biother Radiopharm. 2003;18:853–60.

    Article  PubMed  CAS  Google Scholar 

  36. Wall JS, Kennel SJ, Paulus M, et al. Radioimaging of light chain amyloid with a fibril-reactive monoclonal antibody. J Nucl Med. 2006;47:2016–24.

    PubMed  CAS  Google Scholar 

  37. Wall JS, Paulus MJ, Gleason S, et al. Micro-imaging of amyloid in mice. Methods Enzymol. 2006;412:161–82.

    Article  PubMed  CAS  Google Scholar 

  38. Wall JS, Kennel SJ, Stuckey AC, et al. Radioimmunodetection of amyloid deposits in patients with AL amyloidosis. Blood. 2010;116:2241–4.

    Article  PubMed  CAS  Google Scholar 

  39. Lekakis J, Dimopoulos M, Nanas J, et al. Antimyosin scintigraphy for detection of cardiac amyloidosis. Am J Cardiol. 1997;80:963–5.

    Article  PubMed  CAS  Google Scholar 

Download references

Disclosure

No potential conflicts of interest relevant to this article were reported.

Author information

Authors and Affiliations

  1. Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, 22 South Greene Street, Baltimore, MD, 21201, USA

    Wengen Chen & Vasken Dilsizian

Authors
  1. Wengen Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Vasken Dilsizian
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Wengen Chen.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chen, W., Dilsizian, V. Molecular Imaging of Amyloidosis: Will the Heart Be the Next Target After the Brain?. Curr Cardiol Rep 14, 226–233 (2012). https://doi.org/10.1007/s11886-011-0239-5

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11886-011-0239-5

Keywords

Search

Navigation