Skip to main content
SpringerLink
Log in

New quantitative indices of cardiac amyloidosis with 99mTc-pyrophosphate scintigraphy

  • Original Article
  • Published:
Japanese Journal of Radiology Aims and scope Submit manuscript

Abstract

Purpose

Amyloid light chain (AL) and transthyretin (ATTR) are the major subtypes of cardiac amyloidosis (CA). 99mTc-pyrophosphate (PYP) scintigraphy is used to differentiate ATTR from other CA subtypes. We adapted the standardized uptake value (SUV) for 99mTc-PYP and proposed two quantitative indices, amyloid deposition volume (AmyDV) and total amyloid uptake (TAU). This study aimed to evaluate the utility of these quantitative indices in differentiating ATTR from non-ATTRs.

Materials and methods

Before the SUV measurement, the Becquerel calibration factor (BCF) of 99mTc was obtained by a phantom experiment. Thirty-two patients who had undergone hybrid SPECT/CT imaging 3 h after injection of 99mTc-PYP (370 MBq) were studied. CT attenuation correction for image reconstruction was applied in all. We calculated SUV, AmyDV, and TAU using a quantitative analysis software program for bone SPECT (GI-BONE) and analyzed AmyDV using two methods: threshold method (set 40%); and constant value method (average SUVmax of ribs). We assessed the diagnostic ability of heart-to-contralateral lung (H/CL) ratio, SUV, AmyDV, and TAU to differentiate ATTR from non-ATTR using receiver operating characteristic (ROC) analysis.

Results

Statistically significant differences in all quantitative indices were observed between ATTR and non-ATTR. The area under the curve of each quantitative index for discriminating between ATTR and non-ATTR were as follows: H/CL, 0.997; SUVmax, 0.953; SUVmean (M1), 0.964; SUVmean (M2), 0.969; AmyDV (M1), 0.875; AmyDV (M2), 0.974; and TAU, 0.974. The AmyDV (M2) had higher diagnostic ability than AmyDV (M1). Thus, TAU was calculated as AmyDV (M2) × SUVmean (M2). In the ROC curve, SUV, AmyDV, and TAU had almost the same diagnostic ability as H/CL in distinguishing ATTR from non-ATTRs.

Conclusions

We propose two novel 3D-based quantitative parameters (AmyDV and TAU) that have almost equal ability to discriminate ATTR from non-ATTR.

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
Fig. 4
Fig. 5

Similar content being viewed by others

Data availability

The data that support the findings of this study are available on request from the corresponding author, [HO]. The data are not publicly available due to their containing information that could compromise the privacy of research participants.

References

  1. Tuzovic M, Yang EH, Baas AS, Depasquale EC, Deng MC, Cruz D, et al. Cardiac amyloidosis: diagnosis and treatment strategies. Curr Oncol Rep. 2017;19:46. https://doi.org/10.1007/s11912-017-0607-4.

    Article  CAS  PubMed  Google Scholar 

  2. Hutt DF, Quigley AM, Page J, Hall ML, Burniston M, Gopaul D, et al. Utility and limitations of 3,3-diphosphono-1,2-propanodicarboxylic acid scintigraphy in systemic amyloidosis. Eur Heart J Cardiovasc Imaging. 2014;15:1289–98. https://doi.org/10.1093/ehjci/jeu107.

    Article  PubMed  Google Scholar 

  3. 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. https://doi.org/10.1016/j.jacc.2005.05.073.

    Article  PubMed  Google Scholar 

  4. 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. https://doi.org/10.1161/CIRCIMAGING.112.000132.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Gertz MA, Brown ML, Hauser MF, Kyle RA. Utility of technetium Tc 99m pyrophosphate bone scanning in cardiac amyloidosis. Arch Intern Med. 1987;147:1039–44. https://doi.org/10.1001/archinte.147.6.1039.

    Article  CAS  PubMed  Google Scholar 

  6. 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. https://doi.org/10.1001/jamacardio.2016.2839.

    Article  PubMed  Google Scholar 

  7. Quock TP, Yan T, Chang E, Guthrie S, Broder MS. Epidemiology of AL amyloidosis: a real-world study using US claims data. Blood Adv. 2018;2:1046–53. https://doi.org/10.1182/bloodadvances.2018016402.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Cornwell GG, Murdoch WL, Kyle RA, Westermark P, Pitkänen P. Frequency and distribution of senile cardiovascular amyloid. A clinicopathologic correlation. Am J Med. 1983;75:618–23. https://doi.org/10.1016/0002-9343(83)90443-6.

    Article  PubMed  Google Scholar 

  9. Tanskanen M, Peuralinna T, Polvikoski T, Notkola IL, Sulkava R, Hardy J, et al. Senile systemic amyloidosis affects 25% of the very aged and associates with genetic variation in alpha2-macroglobulin and tau: a population-based autopsy study. Ann Med. 2008;40:232–9. https://doi.org/10.1080/07853890701842988.

    Article  CAS  PubMed  Google Scholar 

  10. Banypersad SM, Sado DM, Flett AS, Gibbs SD, Pinney JH, Maestrini V, et al. Quantification of myocardial extracellular volume fraction in systemic AL amyloidosis: an equilibrium contrast cardiovascular magnetic resonance study. Circ Cardiovasc Imaging. 2013;6:34–9. https://doi.org/10.1161/CIRCIMAGING.112.978627.

    Article  PubMed  Google Scholar 

  11. Oda S, Utsunomiya D, Morita K, Nakaura T, Yuki H, Kidoh M, et al. Cardiovascular magnetic resonance myocardial T1 mapping to detect and quantify cardiac involvement in familial amyloid polyneuropathy. Eur Radiol. 2017;27:4631–8. https://doi.org/10.1007/s00330-017-4845-5.

    Article  PubMed  Google Scholar 

  12. Kotecha T, Martinez-Naharro A, Treibel TA, Francis R, Nordin S, Abdel-Gadir A, et al. Myocardial edema and prognosis in amyloidosis. J Am Coll Cardiol. 2018;71:2919–31. https://doi.org/10.1016/j.jacc.2018.03.536.

    Article  PubMed  Google Scholar 

  13. Ridouani F, Damy T, Tacher V, Derbel H, Legou F, Sifaoui I, et al. Myocardial native T2 measurement to differentiate light-chain and transthyretin cardiac amyloidosis and assess prognosis. J Cardiovasc Magn Reson. 2018;20:58. https://doi.org/10.1186/s12968-018-0478-3.

    Article  PubMed  PubMed Central  Google Scholar 

  14. 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. https://doi.org/10.1161/CIRCULATIONAHA.116.021612.

    Article  CAS  PubMed  Google Scholar 

  15. Ruberg FL, Miller EJ. Nuclear tracers for transthyretin cardiac amyloidosis: time to bone up? Circ Cardiovasc Imaging. 2013;6:162–4. https://doi.org/10.1161/CIRCIMAGING.113.000178.

    Article  PubMed  Google Scholar 

  16. Coutinho MC, Cortez-Dias N, Cantinho G, Conceição I, Oliveira A, Bordalo e Sá A, et al. Reduced myocardial 123-iodine metaiodobenzylguanidine uptake: a prognostic marker in familial amyloid polyneuropathy. Circ Cardiovasc Imaging. 2013;6:627–36. https://doi.org/10.1161/CIRCIMAGING.112.000367.

    Article  PubMed  Google Scholar 

  17. 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. https://doi.org/10.1016/j.jcmg.2014.09.018.

    Article  PubMed  Google Scholar 

  18. 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: e002954. https://doi.org/10.1161/CIRCIMAGING.114.002954.

    Article  PubMed  Google Scholar 

  19. 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. https://doi.org/10.2967/jnumed.115.169870.

    Article  CAS  PubMed  Google Scholar 

  20. Fine NM, Arruda-Olson AM, Dispenzieri A, Zeldenrust SR, Gertz MA, Kyle RA, et al. Yield of noncardiac biopsy for the diagnosis of transthyretin cardiac amyloidosis. Am J Cardiol. 2014;113:1723–7. https://doi.org/10.1016/j.amjcard.2014.02.030.

    Article  CAS  PubMed  Google Scholar 

  21. Quarta CC, Gonzalez-Lopez E, Gilbertson JA, Botcher N, Rowczenio D, Petrie A, et al. Diagnostic sensitivity of abdominal fat aspiration in cardiac amyloidosis. Eur Heart J. 2017;38:1905–8. https://doi.org/10.1093/eurheartj/ehx047.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Ren C, Ren J, Tian Z, Du Y, Hao Z, Zhang Z, et al. Assessment of cardiac amyloidosis with 99mTc-pyrophosphate (PYP) quantitative SPECT. EJNMMI Phys. 2021;8:3. https://doi.org/10.1186/s40658-020-00342-7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Radiology, Tokushima University Hospital, Kuramoto-Cho 2-50-1, Tokushima, 770-8503, Japan

    Noritake Matsuda, Shota Azane, Yamato Kunikane & Masafumi Amano

  2. Department of Medical Imaging/Nuclear Medicine, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan

    Hideki Otsuka

  3. Advance Radiation Research, Education and Management Center, Tokushima University, Tokushima, Japan

    Tamaki Otani

  4. Department of Radiology and Radiation Oncology, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan

    Yoichi Otomi & Masafumi Harada

  5. Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan

    Yuya Ueki

  6. Department of Radiology, Tokushima Red Cross Hospital, Tokushima, Japan

    Masahiro Kubota

  7. Department of Cardiovascular Medicine, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan

    Shusuke Yagi & Masataka Sata

Authors
  1. Noritake Matsuda
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hideki Otsuka
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tamaki Otani
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Shota Azane
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yamato Kunikane
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yoichi Otomi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yuya Ueki
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Masahiro Kubota
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Masafumi Amano
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Shusuke Yagi
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Masataka Sata
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Masafumi Harada
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

HO conceived the idea of the study. NM performed all phantom experiments, clinical data analysis, and described this article. HO and YO interpreted the planar and SPECT images individually. TO, SA, YK, and MA performed the phantom experiment and clinical nuclear medicine examination with technical advice. YU and KM performed the phantom experiment. MS and SY performed clinical diagnosis and suggestion of cardiac disease pathologies. MH performed clinical suggestion. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Hideki Otsuka.

Ethics declarations

Conflict of interest

The authors declare that they have no competing interests.

Ethical approval

This retrospective study was performed at a single university hospital and received approval from the Tokushima University Hospital ethics committee (approval number: 3947).

Informed consent

The requirement of written informed consent was waived.

Consent for publication

The information disclosure document of this study is available to the public on Tokushima University Hospital website.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Matsuda, N., Otsuka, H., Otani, T. et al. New quantitative indices of cardiac amyloidosis with 99mTc-pyrophosphate scintigraphy. Jpn J Radiol 41, 428–436 (2023). https://doi.org/10.1007/s11604-022-01364-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11604-022-01364-0

Keywords

Search

Navigation