Skip to main content

Advertisement

SpringerLink
Log in

Visualization of multiple organ amyloid involvement in systemic amyloidosis using 11C-PiB PET imaging

  • Original Article
  • Published:
European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

To investigate the utility of Pittsburgh compound B (PiB) positron emission tomography (PET) imaging for evaluating whole-body amyloid involvement in patients with systemic amyloidosis.

Methods

Whole-body 11C-PiB PET was performed in seven patients with systemic immunoglobulin light-chain (AL) amyloidosis, seven patients with hereditary transthyretin (ATTRm) amyloidosis, one asymptomatic TTR mutation carrier and three healthy controls. The correlations between clinical organ involvement, radiological 11C-PiB uptake and histopathological findings were analysed for each organ.

Results

Organ involvement on 11C-PiB PET imaging showed good correlations with the clinical findings for the heart and stomach. Abnormal tracer uptake was also observed in the spleen, lachrymal gland, submandibular gland, sublingual gland, lymph node, brain, scalp, extraocular muscles, nasal mucosa, pharynx, tongue and nuchal muscles, most of which were asymptomatic. Physiological tracer uptake was universally observed in the urinary tract (kidney, renal pelvis, ureter and bladder) and enterohepatic circulatory system (liver, gallbladder, bile duct and small intestine) in all participants. Most of the patients and one healthy control subject showed asymptomatic tracer uptake in the lung and parotid gland. The peripheral nervous system did not show any tracer uptake even in patients with apparent peripheral neuropathy. Histological amyloid deposition was confirmed in biopsied myocardium and gastric mucosa where abnormal 11C-PiB retention was observed.

Conclusions

11C-PiB PET imaging can be used clinically in the systemic evaluation of amyloid distribution in patients with AL and ATTRm amyloidosis. Quantitative analysis of 11C-PiB PET images may be useful in therapy evaluation and will reveal whether amyloid clearance is correlated with clinical response.

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
Fig. 3

Similar content being viewed by others

References

  1. Nordberg A, Carter SF, Rinne J, Drzezga A, Brooks DJ, Vandenberghe R, et al. A European multicentre PET study of fibrillar amyloid in Alzheimer's disease. Eur J Nucl Med Mol Imaging. 2013;40:104–14. https://doi.org/10.1007/s00259-012-2237-2.

    Article  CAS  PubMed  Google Scholar 

  2. Johnson KA, Gregas M, Becker JA, Kinnecom C, Salat DH, Moran EK, et al. Imaging of amyloid burden and distribution in cerebral amyloid angiopathy. Ann Neurol. 2007;62:229–34. https://doi.org/10.1002/ana.21164.

    Article  PubMed  Google Scholar 

  3. LeVine H III. Quantification of beta-sheet amyloid fibril structures with thioflavin T. Methods Enzymol. 1999;309:274–84.

    Article  CAS  PubMed  Google Scholar 

  4. Antoni G, Lubberink M, Estrada S, Axelsson J, Carlson K, Lindsjo L, et al. In vivo visualization of amyloid deposits in the heart with 11C-PIB and PET. J Nucl Med. 2013;54:213–20. https://doi.org/10.2967/jnumed.111.102053.

    Article  CAS  PubMed  Google Scholar 

  5. Hellstrom-Lindahl E, Westermark P, Antoni G, Estrada S. In vitro binding of [3H]PIB to human amyloid deposits of different types. Amyloid. 2014;21:21–7. https://doi.org/10.3109/13506129.2013.860895.

    Article  PubMed  Google Scholar 

  6. Sekijima Y, Yazaki M, Oguchi K, Ezawa N, Yoshinaga T, Yamada M, et al. Cerebral amyloid angiopathy in posttransplant patients with hereditary ATTR amyloidosis. Neurology. 2016;87:773–81. https://doi.org/10.1212/wnl.0000000000003001.

    Article  CAS  PubMed  Google Scholar 

  7. Gertz MA, Comenzo R, Falk RH, Fermand JP, Hazenberg BP, Hawkins PN, et al. Definition of organ involvement and treatment response in immunoglobulin light chain amyloidosis (AL): a consensus opinion from the 10th International Symposium on Amyloid and Amyloidosis, Tours, France, 18-22 April 2004, 18-22 April 2004. Am J Hematol. 2005;79:319–28. https://doi.org/10.1002/ajh.20381.

  8. Sekijima Y, Uchiyama S, Tojo K, Sano K, Shimizu Y, Imaeda T, et al. High prevalence of wild-type transthyretin deposition in patients with idiopathic carpal tunnel syndrome: a common cause of carpal tunnel syndrome in the elderly. Hum Pathol. 2011;42:1785–91. https://doi.org/10.1016/j.humpath.2011.03.004.

    Article  PubMed  Google Scholar 

  9. Scheinin NM, Tolvanen TK, Wilson IA, Arponen EM, Nagren KA, Rinne JO. Biodistribution and radiation dosimetry of the amyloid imaging agent 11C-PIB in humans. J Nucl Med. 2007;48:128–33.

    CAS  PubMed  Google Scholar 

  10. 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. https://doi.org/10.1056/nejm199008233230803.

    Article  CAS  PubMed  Google Scholar 

  11. Rydh A, Suhr O, Hietala SO, Ahlstrom KR, Pepys MB, Hawkins PN. Serum amyloid P component scintigraphy in familial amyloid polyneuropathy: regression of visceral amyloid following liver transplantation. Eur J Nucl Med. 1998;25:709–13.

    Article  CAS  PubMed  Google Scholar 

  12. Nelson SR, Hawkins PN, Richardson S, Lavender JP, Sethi D, Gower PE, et al. Imaging of haemodialysis-associated amyloidosis with 123I-serum amyloid P component. Lancet. 1991;338:335–9.

    Article  CAS  PubMed  Google Scholar 

  13. Rowczenio D, Dogan A, Theis JD, Vrana JA, Lachmann HJ, Wechalekar AD, et al. Amyloidogenicity and clinical phenotype associated with five novel mutations in apolipoprotein A-I. Am J Pathol. 2011;179:1978–87. https://doi.org/10.1016/j.ajpath.2011.06.024.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Hutt DF, Gilbertson J, Quigley AM, Wechalekar AD. (99m)Tc-DPD scintigraphy as a novel imaging modality for identification of skeletal muscle amyloid deposition in light-chain amyloidosis. Amyloid. 2016;23:134–5. https://doi.org/10.3109/13506129.2016.1158160.

    Article  PubMed  Google Scholar 

  15. Puille M, Altland K, Linke RP, Steen-Muller MK, Kiett R, Steiner D, et al. 99mTc-DPD scintigraphy in transthyretin-related familial amyloidotic polyneuropathy. Eur J Nucl Med Mol Imaging. 2002;29:376–9.

    Article  CAS  PubMed  Google Scholar 

  16. Quarta CC, Obici L, Guidalotti PL, Pieroni M, Longhi S, Perlini S, et al. High 99mTc-DPD myocardial uptake in a patient with apolipoprotein AI-related amyloidotic cardiomyopathy. Amyloid. 2013;20:48–51. https://doi.org/10.3109/13506129.2012.746938.

    Article  PubMed  Google Scholar 

  17. Rao BK, Padmalatha C, Au Buchon J, Lieberman LM. Hepatic and splenic scintigraphy in idiopathic systemic amyloidosis. Eur J Nucl Med. 1981;6:143–6.

    Article  CAS  PubMed  Google Scholar 

  18. Janssen S, Piers DA, van Rijswijk MH, Meijer S, Mandema E. Soft-tissue uptake of 99mTc-diphosphonate and 99mTc-pyrophosphate in amyloidosis. Eur J Nucl Med. 1990;16:663–70.

    Article  CAS  PubMed  Google Scholar 

  19. Bokhari S, Castano 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. https://doi.org/10.1161/circimaging.112.000132.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Nakagawa M, Sekijima Y, Yazaki M, Tojo K, Yoshinaga T, Doden T, et al. Carpal tunnel syndrome: a common initial symptom of systemic wild-type ATTR (ATTRwt) amyloidosis. Amyloid. 2016;23:58–63. https://doi.org/10.3109/13506129.2015.1135792.

    Article  CAS  PubMed  Google Scholar 

  21. 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. https://doi.org/10.1007/s00259-014-2787-6.

    Article  CAS  PubMed  Google Scholar 

  22. Osborne DR, Acuff SN, Stuckey A, Wall JS. A routine PET/CT protocol with streamlined calculations for assessing cardiac amyloidosis using (18)F-florbetapir. Front Cardiovasc Med. 2015;2:23. https://doi.org/10.3389/fcvm.2015.00023.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Broski SM, Spinner RJ, Howe BM, Dispenzieri A, Johnson GB. 18F-Florbetapir and 18F-FDG PET/CT in systemic immunoglobulin light chain amyloidosis involving the peripheral nerves. Clin Nucl Med. 2016;41:e115–7. https://doi.org/10.1097/rlu.0000000000000947.

    Article  PubMed  Google Scholar 

  24. García-González P, Sánchez-Jurado R, Cozar-Santiago MP, Ferrando-Beltrán M, Pérez-Rodriguez PL, Ferrer-Rebolleda J. Laryngeal and cardiac amyloidosis diagnosed by 18F-Florbetapir PET/CT. Rev Esp Med Nucl Imagen Mol. 2017;36:135–6. https://doi.org/10.1016/j.remn.2016.03.006.

    PubMed  Google Scholar 

  25. Leung N, Ramirez-Alvarado M, Nasr SH, Kemp BJ, Johnson GB. Detection of ALECT2 amyloidosis by positron emission tomography-computed tomography imaging with florbetapir. Br J Haematol. 2017;177:12. https://doi.org/10.1111/bjh.14519.

    Article  PubMed  Google Scholar 

  26. D'Estanque E, Chambert B, Moranne O, Kotzki PO, Boudousq V. 18F-Florbetaben: a new tool for amyloidosis staging? Clin Nucl Med. 2017;42:50–3. https://doi.org/10.1097/rlu.0000000000001434.

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  28. Schaadt BK, Hendel HW, Gimsing P, Jonsson V, Pedersen H, Hesse B. 99mTc-aprotinin scintigraphy in amyloidosis. J Nucl Med. 2003;44:177–83.

    PubMed  Google Scholar 

  29. Hawkins PN, Pepys MB. Imaging amyloidosis with radiolabelled SAP. Eur J Nucl Med. 1995;22:595–9.

    Article  CAS  PubMed  Google Scholar 

  30. Bokhari S, Shahzad R, Castano A, Maurer MS. Nuclear imaging modalities for cardiac amyloidosis. J Nucl Cardiol. 2014;21:175–84. https://doi.org/10.1007/s12350-013-9803-2.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Ohyama T, Shimokama T, Yoshikawa Y, Watanabe T. Splenic amyloidosis: correlations between chemical types of amyloid protein and morphological features. Mod Pathol. 1990;3:419–22.

    CAS  PubMed  Google Scholar 

  32. Martins AC, Rosa AM, Costa E, Tavares C, Quadrado MJ, Murta JN. Ocular manifestations and therapeutic options in patients with familial amyloid polyneuropathy: a systematic review. Biomed Res Int. 2015;2015:282405. https://doi.org/10.1155/2015/282405.

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Hachulla E, Janin A, Flipo RM, Saile R, Facon T, Bataille D, et al. Labial salivary gland biopsy is a reliable test for the diagnosis of primary and secondary amyloidosis. A prospective clinical and immunohistologic study in 59 patients. Arthritis Rheum. 1993;36:691–7.

    Article  CAS  PubMed  Google Scholar 

  34. de Paula EF, de Mello BL, de Carvalho DL, Della-Guardia B, de Almeida MD, Marins LV, et al. Minor salivary gland biopsy for the diagnosis of familial amyloid polyneuropathy. Neurol Sci. 2017;38:311–8. https://doi.org/10.1007/s10072-016-2760-1.

    Article  Google Scholar 

  35. Villa F, Dionigi G, Tanda ML, Rovera F, Boni L. Amyloid goiter. Int J Surg. 2008;6(Suppl 1):S16–8. https://doi.org/10.1016/j.ijsu.2008.12.025.

    Article  PubMed  Google Scholar 

  36. Matsuda M, Gono T, Shimojima Y, Yoshida T, Katoh N, Hoshii Y, et al. AL amyloidosis manifesting as systemic lymphadenopathy. Amyloid. 2008;15:117–24. https://doi.org/10.1080/13506120802006047.

    Article  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  38. Matsuda M, Katoh N, Ikeda S. Clinical manifestations at diagnosis in Japanese patients with systemic AL amyloidosis: a retrospective study of 202 cases with a special attention to uncommon symptoms. Intern Med. 2014;53:403–12.

    Article  PubMed  Google Scholar 

Download references

Funding

This study was funded by a Grant-in-aid for Scientific Research (C) (23,591,237 to Y.S.) from the Japan Society for the Promotion of Science, a grant from the Amyloidosis Research Committee, the Ministry of Health, Labour and Welfare, Japan, and 2015 Global ASPIRE TTR-FAP Competitive Research Grant Award from Pfizer, Inc.

Author information

Authors and Affiliations

  1. Department of Medicine (Neurology and Rheumatology), Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, 390-8621, Japan

    Naoki Ezawa, Nagaaki Katoh, Tsuneaki Yoshinaga & Yoshiki Sekijima

  2. Jisenkai Brain Imaging Research Center, 2-5-1 Honjyo, Matsumoto, Japan

    Kazuhiro Oguchi & Yoshiki Sekijima

  3. Department of Biomedical Laboratory Sciences, Shinshu University School of Health Sciences, 3-1-1 Asahi, Matsumoto, Japan

    Masahide Yazaki

  4. Institute for Biomedical Sciences, Shinshu University, 3-1-1 Asahi, Matsumoto, Japan

    Masahide Yazaki & Yoshiki Sekijima

Authors
  1. Naoki Ezawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nagaaki Katoh
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kazuhiro Oguchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Tsuneaki Yoshinaga
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Masahide Yazaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yoshiki Sekijima
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nagaaki Katoh.

Ethics declarations

Conflicts of interest

None.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the principles of the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ezawa, N., Katoh, N., Oguchi, K. et al. Visualization of multiple organ amyloid involvement in systemic amyloidosis using 11C-PiB PET imaging. Eur J Nucl Med Mol Imaging 45, 452–461 (2018). https://doi.org/10.1007/s00259-017-3814-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00259-017-3814-1

Keywords

Search

Navigation