Skip to main content

Advertisement

SpringerLink
Log in

Comparison of 18F-sodium fluoride uptake in the whole bone, pelvis, and femoral neck of multiple myeloma patients before and after high-dose therapy and conventional-dose chemotherapy

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

Abstract

Aim

To compare the effects of high-dose therapy (HDT consisting of high-dose chemotherapy followed by autologous stem cell transplantation) and conventional-dose chemotherapy (non-HDT) on the uptake of 18F-sodium fluoride (NaF) in the whole bone, pelvis, and femoral neck of multiple myeloma (MM) patients.

Method

The data of 19 MM patients who received HDT (61.5 (SD 5.6) years) and 11 MM patients who received conventional-dose chemotherapy (70.9 (SD 7.2) years) were collected in a prospective study. NaF PET/CT imaging was performed at baseline, and 8 weeks and 2 weeks after treatment for the HDT group and the non-HDT group, respectively. A CT-based algorithm was applied to segment the bones, and the global mean SUV (GSUVmean) of the whole bone and pelvis was calculated (OsiriX MD v.9.0, Pixmeo SARL; Bernex, Switzerland). In addition, regions of interest for the whole, medial, and lateral femoral neck were delineated bilaterally. Whole bone and pelvis measurements were replicated by two observers.

Results

The average GSUVmean in the whole bone and pelvis of the patients who underwent HDT significantly decreased from before to after treatment (− 16.27%, p = 0.02 and − 16.54%, p = 0.01, respectively). A significant decrease in the whole and lateral femoral neck was also observed bilaterally in the HDT group. No significant decrease in average GSUVmean was observed in the non-HDT group. A high level of inter-observer reliability was found in intra-class correlation (ICC for pre-treatment whole bone 0.983, post-treatment whole bone 0.989, pre-treatment whole pelvis 0.998, post-treatment whole pelvis 0.996).

Conclusion

NaF uptake significantly decreased after treatment in patients who received high-dose therapy. A high level of agreement was observed between two operators for whole bone and pelvis measurements.

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

References

  1. Walker RE, Lawson MA, Buckle CH, Snowden JA, Chantry AD. Myeloma bone disease: pathogenesis, current treatments and future targets. Br Med Bull. 2014;111:117–38. https://doi.org/10.1093/bmb/ldu016.

    Article  CAS  PubMed  Google Scholar 

  2. Silvestris F, Cafforio P, Calvani N, Dammacco F. Impaired osteoblastogenesis in myeloma bone disease: role of upregulated apoptosis by cytokines and malignant plasma cells. Br J Haematol. 2004;126:475–86. https://doi.org/10.1111/j.1365-2141.2004.05084.x.

    Article  PubMed  Google Scholar 

  3. Zadeh MZ, Raynor W, Oestergaard B, Taghvaei R, Acosta-Montenegro O, Seraj SM, et al. Changes in bone marrow FDG uptake in multiple myeloma patients before and after treatment. J Nucl Med. 2018;59:1430.

    Article  Google Scholar 

  4. Carlson K, Simonsson B, Ljunghall S. Acute effects of high-dose chemotherapy followed by bone marrow transplantation on serum markers of bone metabolism. Calcif Tissue Int. 1994;55:408–11.

    Article  CAS  Google Scholar 

  5. Katz IA, Epstein S. Perspectives: posttransplantation bone disease. J Bone Miner Res. 1992;7:123–6.

    Article  CAS  Google Scholar 

  6. Banfi A, Podestà M, Fazzuoli L, Roberto Sertoli M, Venturini M, Santini G, et al. High-dose chemotherapy shows a dose-dependent toxicity to bone marrow osteoprogenitors. Cancer. 2001;92:2419–28. https://doi.org/10.1002/1097-0142(20011101)92:9<2419::Aid-cncr1591>3.0.Co;2-k.

    Article  CAS  PubMed  Google Scholar 

  7. Czernin J, Satyamurthy N, Schiepers C. Molecular mechanisms of bone 18F-NaF deposition. J Nucl Med. 2010;51:1826.

    Article  CAS  Google Scholar 

  8. Raynor W, Houshmand S, Gholami S, Emamzadehfard S, Rajapakse CS, Blomberg BA, et al. Evolving role of molecular imaging with (18)F-sodium fluoride PET as a biomarker for calcium metabolism. Curr Osteopor Rep. 2016;14:115–25. https://doi.org/10.1007/s11914-016-0312-5.

    Article  Google Scholar 

  9. Costeas A, Woodard HQ, Laughlin JS. Depletion of 18F from blood flowing through bone. J Nucl Med. 1970;11:43–5.

    CAS  PubMed  Google Scholar 

  10. Reilly CC, Raynor WY, Hong AL, Kargilis DC, Lee JS, Alecxih AG, et al. Diagnosis and monitoring of osteoporosis with (18)F-sodium fluoride PET: an unavoidable path for the foreseeable future. Semin Nucl Med. 2018;48:535–40. https://doi.org/10.1053/j.semnuclmed.2018.07.007.

    Article  PubMed  Google Scholar 

  11. Blake GM, Puri T, Siddique M, Frost ML, AEB M, Fogelman I. Site specific measurements of bone formation using [(18)F] sodium fluoride PET/CT. Quant Imaging Med Surg. 2018;8:47–59. https://doi.org/10.21037/qims.2018.01.02.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Ayubcha C, Raynor W, Werner T, Alavi A. Evolving role of NaF-PET in the diagnosis and treatment of osteoporosis. J Nucl Med. 2017;58:1007.

    Google Scholar 

  13. Jassel IS, Siddique M, Frost ML, AEB M, Puri T, Blake GM. The influence of CT and dual-energy X-ray absorptiometry (DXA) bone density on quantitative [(18)F] sodium fluoride PET. Quant Imaging Med Surg. 2019;9:201–9. https://doi.org/10.21037/qims.2019.01.01.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Ayubcha C, Zirakchian Zadeh M, Stochkendahl MJ, Al-Zaghal A, Hartvigsen J, Rajapakse CS, et al. Quantitative evaluation of normal spinal osseous metabolism with 18F-NaF PET/CT. Nucl Med Commun. 2018;39:945–50. https://doi.org/10.1097/mnm.0000000000000891.

    Article  PubMed  Google Scholar 

  15. Ak İ, Onner H, Akay OM. Is there any complimentary role of F-18 NaF PET/CT in detecting of osseous involvement of multiple myeloma? A comparative study for F-18 FDG PET/CT and F-18 FDG NaF PET/CT. Ann Hematol. 2015;94:1567–75.

    Article  CAS  Google Scholar 

  16. Bhutani M, Turkbey B, Tan E, Korde N, Kwok M, Manasanch EE, et al. Bone marrow abnormalities and early bone lesions in multiple myeloma and its precursor disease: a prospective study using functional and morphologic imaging. Leuk Lymphoma. 2016;57:1114–21.

    Article  Google Scholar 

  17. Sadic M, Houshmand S, Alavi A. A new technique: quantitative global disease assessment of FDG-PET/CT. J Clin Anal Med. 2015;6(3).

  18. Oestergaard B. Functional imaging in multiple myeloma -PET/CT and diffusion weighted imaging in multiple myeloma (FULIMA). 2014. https://clinicaltrials.gov/ct2/show/NCT02187731.

  19. Beheshti M, Mottaghy FM, Paycha F, Behrendt FFF, Van den Wyngaert T, Fogelman I, et al. (18)F-NaF PET/CT: EANM procedure guidelines for bone imaging. Eur J Nucl Med Mol Imaging. 2015;42:1767–77. https://doi.org/10.1007/s00259-015-3138-y.

    Article  CAS  PubMed  Google Scholar 

  20. Boellaard R, Delgado-Bolton R, Oyen WJG, Giammarile F, Tatsch K, Eschner W, et al. FDG PET/CT: EANM procedure guidelines for tumour imaging: version 2.0. Eur J Nucl Med Mol Imaging. 2015;42:328–54. https://doi.org/10.1007/s00259-014-2961-x.

    Article  CAS  PubMed  Google Scholar 

  21. Raynor W, Ayubcha C, Shamchi SP, Zadeh MZ, Emamzadehfard S, Werner T, et al. Assessing global uptake of 18F-sodium fluoride in the femoral neck: a novel quantitative technique to evaluate changes in bone turnover with age. J Nucl Med. 2017;58:1223.

    Google Scholar 

  22. Raynor W, Houshmand S, Gholami S, Werner T, Alavi A. Assessment of bone turnover by measuring global uptake of 18F-sodium fluoride in the femoral neck, a novel method for early detection of osteoporosis. J Nucl Med. 2016;57:1769.

    Google Scholar 

  23. Gandhi MK, Lekamwasam S, Inman I, Kaptoge S, Sizer L, Love S, et al. Significant and persistent loss of bone mineral density in the femoral neck after haematopoietic stem cell transplantation: long-term follow-up of a prospective study. Br J Haematol. 2003;121:462–8. https://doi.org/10.1046/j.1365-2141.2003.04303.x.

    Article  PubMed  Google Scholar 

  24. Kang MI, Lee WY, Oh KW, Han JH, Song KH, Cha BY, et al. The short-term changes of bone mineral metabolism following bone marrow transplantation. Bone. 2000;26:275–9.

    Article  CAS  Google Scholar 

  25. Schulte C, Beelen DW, Schaefer UW, Mann K. Bone loss in long-term survivors after transplantation of hematopoietic stem cells: a prospective study. Osteopor Int. 2000;11:344–53. https://doi.org/10.1007/s001980070124.

    Article  CAS  Google Scholar 

  26. Laroche M, Lemaire O, Bourin P, Corre J, Gadelorge M, Roussel M, et al. Dual-energy X-ray absorptiometry and biochemical markers of bone turnover after autologous stem cell transplantation in myeloma. Eur J Haematol. 2012;88:388–95. https://doi.org/10.1111/j.1600-0609.2012.01751.x.

    Article  CAS  PubMed  Google Scholar 

  27. Sachpekidis C, Hillengass J, Goldschmidt H, Wagner B, Haberkorn U, Kopka K, et al. Treatment response evaluation with (18)F-FDG PET/CT and (18)F-NaF PET/CT in multiple myeloma patients undergoing high-dose chemotherapy and autologous stem cell transplantation. Eur J Nucl Med Mol Imaging. 2017;44:50–62. https://doi.org/10.1007/s00259-016-3502-6.

    Article  CAS  PubMed  Google Scholar 

  28. Blake GM, Siddique M, Frost ML, Moore AE, Fogelman I. Imaging of site specific bone turnover in osteoporosis using positron emission tomography. Curr Osteopor Rep. 2014;12:475–85.

    Article  Google Scholar 

  29. Rohren EM, Etchebehere EC, Araujo JC, Hobbs BP, Swanston NM, Everding M, et al. Determination of skeletal tumor burden on 18F-fluoride PET/CT. J Nucl Med. 2015;56:1507–12.

    Article  CAS  Google Scholar 

  30. Oldan JD, Hawkins AS, Chin BB. 18F sodium fluoride PET/CT in patients with prostate cancer: quantification of normal tissues, benign degenerative lesions, and malignant lesions. World J Nucl Med. 2016;15:102.

    Article  Google Scholar 

  31. Boellaard R, Krak NC, Hoekstra OS, Lammertsma AA. Effects of noise, image resolution, and ROI definition on the accuracy of standard uptake values: a simulation study. J Nucl Med. 2004;45:1519–27.

    PubMed  Google Scholar 

  32. Krak NC, Boellaard R, Hoekstra OS, Twisk JW, Hoekstra CJ, Lammertsma AA. Effects of ROI definition and reconstruction method on quantitative outcome and applicability in a response monitoring trial. Eur J Nucl Med Mol Imaging. 2005;32:294–301. https://doi.org/10.1007/s00259-004-1566-1.

    Article  PubMed  Google Scholar 

  33. Vanderhoek M, Perlman SB, Jeraj R. Impact of the definition of peak standardized uptake value on quantification of treatment response. J Nucl Med. 2012;53:4–11.

    Article  CAS  Google Scholar 

  34. Zadeh MZ, Raynor WY, Seraj SM, Ayubcha C, Kothekar E, Werner T, et al. Evolving roles of fluorodeoxyglucose and sodium fluoride in assessment of multiple myeloma patients: introducing a novel method of PET quantification to overcome shortcomings of the existing approaches. PET Clin. 2019;14(3):341–352. https://doi.org/10.1016/j.cpet.2019.03.004.

  35. Raynor WY, Zadeh MZ, Kothekar E, Yellanki DP, Alavi A. Evolving role of PET-based novel quantitative techniques in the management of hematological malignancies. PET Clin. 2019;14(3):331–340. https://doi.org/10.1016/j.cpet.2019.03.003.

  36. Lin C, Bradshaw T, Perk T, Harmon S, Eickhoff J, Jallow N, et al. Repeatability of quantitative 18F-NaF PET: a multicenter study. J Nucl Med. 2016;57:1872–9. https://doi.org/10.2967/jnumed.116.177295.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Brito AE, Santos A, Sasse AD, Cabello C, Oliveira P, Mosci C, et al. 18F-Fluoride PET/CT tumor burden quantification predicts survival in breast cancer. Oncotarget. 2017;8:36001–11. https://doi.org/10.18632/oncotarget.16418.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Letellier A, Johnson AC, Kit NH, Savigny JF, Batalla A, Parienti JJ, et al. Uptake of radium-223 dichloride and early [(18)F] NaF PET response are driven by baseline [(18)F]NaF parameters: a pilot study in castration-resistant prostate cancer patients. Mol Imaging Biol. 2018;20:482–91. https://doi.org/10.1007/s11307-017-1132-4.

    Article  CAS  PubMed  Google Scholar 

  39. Unnanuntana A, Gladnick BP, Donnelly E, Lane JM. The assessment of fracture risk. J Bone Joint Surg Am. 2010;92:743–53. https://doi.org/10.2106/jbjs.I.00919.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Gandhi MK, Lekamwasam S, Inman I, Kaptoge S, Sizer L, Love S, et al. Significant and persistent loss of bone mineral density in the femoral neck after haematopoietic stem cell transplantation: long-term follow-up of a prospective study. Br J Haematol. 2003;121:462–8.

    Article  Google Scholar 

  41. Clark RE, Flory AJ, Ion EM, Woodcock BE, Durham BH, Fraser WD. Biochemical markers of bone turnover following high-dose chemotherapy and autografting in multiple myeloma. Blood. 2000;96:2697–702.

    Article  CAS  Google Scholar 

  42. Terpos E, Politou M, Szydlo R, Nadal E, Avery S, Olavarria E, et al. Autologous stem cell transplantation normalizes abnormal bone remodeling and sRANKL/osteoprotegerin ratio in patients with multiple myeloma. Leukemia. 2004;18:1420.

    Article  CAS  Google Scholar 

Download references

Funding

This project was funded by the Region of Southern Denmark, University of Southern Denmark, Odense University Hospital, Harboe Foundation, The A.P. Møller Foundation (Fonden til lægevidenskabens fremme), Aase & Ejnar Danielsen Foundation, and The Family Hede Nielsen Foundation.

Author information

Authors and Affiliations

  1. Department of Radiology, Hospital of the University of Pennsylvania, 3400 Spruce St, Philadelphia, PA, 19104, USA

    Mahdi Zirakchian Zadeh, William Y. Raynor, Mona-Elisabeth Revheim, Siavash Mehdizadeh Seraj, Oswaldo Acosta-Montenegro, Cyrus Ayubcha, Dani P. Yellanki, Abdullah Al-Zaghal, Thomas J. Werner & Abass Alavi

  2. Department of Radiology, Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Mahdi Zirakchian Zadeh & Hongming Zhuang

  3. Department of Hematology, Odense University Hospital, Odense, Denmark

    Brian Østergaard & Niels Abildgaard

  4. Drexel University College of Medicine, Philadelphia, PA, USA

    William Y. Raynor

  5. Division of Radiology and Nuclear Medicine, Oslo University Hospital, Oslo, Norway

    Mona-Elisabeth Revheim

  6. Faculty of Medicine, University of Oslo, Oslo, Norway

    Mona-Elisabeth Revheim

  7. Department of Nuclear Medicine, Odense University Hospital, Odense, Denmark

    Anne L. Nielsen, Caius M. Constantinescu, Oke Gerke & Poul Flemming Høilund-Carlsen

Authors
  1. Mahdi Zirakchian Zadeh
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Brian Østergaard
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. William Y. Raynor
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mona-Elisabeth Revheim
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Siavash Mehdizadeh Seraj
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Oswaldo Acosta-Montenegro
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Cyrus Ayubcha
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Dani P. Yellanki
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Abdullah Al-Zaghal
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Anne L. Nielsen
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Caius M. Constantinescu
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Oke Gerke
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Thomas J. Werner
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Hongming Zhuang
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Niels Abildgaard
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Poul Flemming Høilund-Carlsen
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Abass Alavi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Abass Alavi.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethics

The protocol was approved by the Danish Ethics Committee (S-20120209), the Danish Data Protection Agency (2008-58-0035) and registered at clinicaltrials.gov (NCT02187731).

Informed consent

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

Additional information

Publisher’s note

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

This article is part of the Topical Collection on Hematology

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zirakchian Zadeh, M., Østergaard, B., Raynor, W.Y. et al. Comparison of 18F-sodium fluoride uptake in the whole bone, pelvis, and femoral neck of multiple myeloma patients before and after high-dose therapy and conventional-dose chemotherapy. Eur J Nucl Med Mol Imaging 47, 2846–2855 (2020). https://doi.org/10.1007/s00259-020-04768-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00259-020-04768-0

Keywords

Search

Navigation