pp 1–8 | Cite as

68Ga-DOTANOC and 18F-FDG PET/CT in metastatic medullary thyroid carcinoma: novel correlations with tumoral biomarkers

  • Pedro SouteiroEmail author
  • Patrícia Gouveia
  • Gonçalo Ferreira
  • Sandra Belo
  • Cláudia Costa
  • Davide Carvalho
  • Hugo Duarte
  • Inês Lucena Sampaio
Original Article



Metastatic disease is common in medullary thyroid carcinoma (MTC) and it is usually detected by raising calcitonin and carcinoembryonic antigen (CEA) levels. Nuclear medicine imaging has an important role in lesion identification/characterisation. We aim to compare 68Ga-DOTANOC PET/CT and 18F-FDG PET/CT performance and to explore the correlations between tumoral markers and functional imaging.


This a retrospective cross-sectional study including 13 patients with MTC and high calcitonin/CEA levels that underwent both 68Ga-DOTANOC PET/CT and 18F-FDG PET/CT.


68Ga-DOTANOC PET/CT identified MTC metastases in 2twopatients that were 18F-FDG-negative (sensitivity of 69.2% vs. 53.9%, respectively). 68Ga-DOTANOC PET/CT also detected a higher number of lesions than 18F-FDG PET/CT in seven patients, with only one patient showing the opposite pattern. Both differences lacked statistical significance (p = 0.50 and p = 0.86, respectively) but 68Ga-DOTANOC PET/CT better performance allowed changes in patients’ management. 68Ga-positive/18F-FDG-negative patients were the ones with the lowest calcitonin doubling time and presented a CEA doubling time >24 months, while the patient with more 18F-FDG-positive lesions was the one with the highest CEA/calcitonin ratio. The number of lesions found in 68Ga-DOTANOC PET/CT were correlated with calcitonin levels (r = 0.73; p < 0.01) but not with CEA ones (r = 0.42; p = 0.15). The number of 18F-FDG hypermetabolic focus were correlated with CEA levels (r = 0.60; p < 0.05) but not with calcitonin (r = 0.48; p = 0.09).


This is the first study to describe a positive correlation between 68Ga-positive lesions and calcitonin levels and between 18F-FDG-positivity and CEA levels. Tumoral markers pattern in metastatic MTC could help clinicians to decide which exam to perform first.


Thyroid cancer, medullary PET-CT Scan Calcitonin Carcinoembryonic antigen 


Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.

Ethical approval

All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. All patients gave their consent to be enroled in this study.


  1. 1.
    S.A. Wells Jr., S.L. Asa, H. Dralle, R. Elisei, D.B. Evans, R.F. Gagel et al. Revised American Thyroid Association guidelines for the management of medullary thyroid carcinoma. Thyroid 25, 567–610 (2015)CrossRefGoogle Scholar
  2. 2.
    F. Pacini, M.G. Castagna, C. Cipri, M. Schlumberger, Medullary thyroid carcinoma. Clin. Oncol. (R. Coll. Radiol.) 22, 475–485 (2010)CrossRefGoogle Scholar
  3. 3.
    J. Schmidt Jensen, C. Gronhoj, C. Mirian, D.H. Jensen, J. Friborg, C.H. Hahn et al. Incidence and survival of thyroid cancer in children, adolescents, and young adults in Denmark: A Nationwide Study from 1980 to 2014. Thyroid 28, 1128–1133 (2018)CrossRefGoogle Scholar
  4. 4.
    F. Torresan, E. Cavedon, C. Mian, M. Iacobone, Long-term outcome after surgery for medullary thyroid carcinoma: A single-center experience. World J. Surg. 42, 367–375 (2018)CrossRefGoogle Scholar
  5. 5.
    A. Machens, J. Ukkat, S. Hauptmann, H. Dralle, Abnormal carcinoembryonic antigen levels and medullary thyroid cancer progression: a multivariate analysis. Arch. Surg. (Chic., Ill: 1960) 142, 289–293 (2007). (discussion 294)Google Scholar
  6. 6.
    K. Saltiki, G. Rentziou, K. Stamatelopoulos, G. Georgiopoulos, C. Stavrianos, E. Lambrinoudaki et al. Small medullary thyroid carcinoma: post-operative calcitonin rather than tumour size predicts disease persistence and progression. Eur. J. Endocrinol. 171, 117–126 (2014)CrossRefGoogle Scholar
  7. 7.
    A. Laure Giraudet, A. Al Ghulzan, A. Auperin, S. Leboulleux, A. Chehboun, F. Troalen et al. Progression of medullary thyroid carcinoma: assessment with calcitonin and carcinoembryonic antigen doubling times. Eur. J. Endocrinol. 158, 239–246 (2008)CrossRefGoogle Scholar
  8. 8.
    M.F. Bozkurt, I. Virgolini, S. Balogova, M. Beheshti, D. Rubello, C. Decristoforo et al. Guideline for PET/CT imaging of neuroendocrine neoplasms with (68)Ga-DOTA-conjugated somatostatin receptor targeting peptides and (18)F-DOPA. Eur. J. Nucl. Med. Mol. Imaging 44, 1588–1601 (2017)CrossRefGoogle Scholar
  9. 9.
    G. Treglia, P. Castaldi, M.F. Villani, G. Perotti, C. de Waure, A. Filice et al. Comparison of 18F-DOPA, 18F-FDG and 68Ga-somatostatin analogue PET/CT in patients with recurrent medullary thyroid carcinoma. Eur. J. Nucl. Med. Mol. Imaging 39, 569–580 (2012)CrossRefGoogle Scholar
  10. 10.
    B.G. Conry, N.D. Papathanasiou, V. Prakash, I. Kayani, M. Caplin, S. Mahmood et al. Comparison of (68)Ga-DOTATATE and (18)F-fluorodeoxyglucose PET/CT in the detection of recurrent medullary thyroid carcinoma. Eur. J. Nucl. Med. Mol. Imaging 37, 49–57 (2010)CrossRefGoogle Scholar
  11. 11.
    E. Mato, X. Matias-Guiu, A. Chico, S.M. Webb, R. Cabezas, L. Berna et al. Somatostatin and somatostatin receptor subtype gene expression in medullary thyroid carcinoma. J. Clin. Endocrinol. Metab. 83, 2417–2420 (1998)Google Scholar
  12. 12.
    M.O. Oksuz, L. Winter, C. Pfannenberg, G. Reischl, K. Mussig, R. Bares et al. Peptide receptor radionuclide therapy of neuroendocrine tumors with (90)Y-DOTATOC: is treatment response predictable by pre-therapeutic uptake of (68)Ga-DOTATOC? Diagn. Interv. Imaging 95, 289–300 (2014)CrossRefGoogle Scholar
  13. 13.
    E. Hindié, The NETPET Score: Combining FDG and somatostatin receptor imaging for optimal management of patients with metastatic well-differentiated neuroendocrine tumors. Theranostics 7, 1159–1163 (2017)CrossRefGoogle Scholar
  14. 14.
    G. Treglia, V. Rufini, M. Salvatori, A. Giordano, L. Giovanella, PET imaging in Recurrent Medullary Thyroid Carcinoma. Int. J. Mol. Imaging 2012, 324686 (2012)Google Scholar
  15. 15.
    A. Miyauchi, T. Onishi, S. Morimoto, S. Takai, F. Matsuzuka, K. Kuma et al. Relation of doubling time of plasma calcitonin levels to prognosis and recurrence of medullary thyroid carcinoma. Ann. Surg. 199, 461–466 (1984)CrossRefGoogle Scholar
  16. 16.
    R.M. Tuttle, B. Haugen, N.D. Perrier, Updated American Joint Committee on cancer/tumor-node-metastasis staging system for differentiated and anaplasticthyroid cancer (eighth edition): What changed and why? Thyroid 27, 751–756 (2017)CrossRefGoogle Scholar
  17. 17.
    N. Naswa, P. Sharma, S. Suman Kc, S. Lata, R. Kumar, A. Malhotra et al. Prospective evaluation of 68Ga-DOTA-NOC PET-CT in patients with recurrent medullary thyroid carcinoma: comparison with 18F-FDG PET-CT. Nucl. Med. Commun. 33, 766–774 (2012)CrossRefGoogle Scholar
  18. 18.
    Z.G. Ozkan, S. Kuyumcu, A.K. Uzum, M.F. Gecer, S. Ozel, F. Aral et al. Comparison of (6)(8)Ga-DOTATATE PET-CT, (1)(8)F-FDG PET-CT and 99mTc-(V)DMSA scintigraphy in the detection of recurrent or metastatic medullary thyroid carcinoma. Nucl. Med. Commun. 36, 242–250 (2015)CrossRefGoogle Scholar
  19. 19.
    K. Kilian, (68)Ga-DOTA and analogs: Current status and future perspectives. Rep. Pract. Oncol. Radiother. 19, S13–S21 (2014)CrossRefGoogle Scholar
  20. 20.
    A. Mojtahedi, S. Thamake, I. Tworowska, D. Ranganathan, E.S. Delpassand, The value of (68)Ga-DOTATATE PET/CT in diagnosis and management of neuroendocrine tumors compared to current FDA approved imaging modalities: a review of literature. Am. J. Nucl. Med. Mol. Imaging 4, 426–434 (2014)Google Scholar
  21. 21.
    M. Papotti, U. Kumar, M. Volante, C. Pecchioni, Y.C. Patel, Immunohistochemical detection of somatostatin receptor types 1-5 in medullary carcinoma of the thyroid. Clin. Endocrinol. (Oxf.). 54, 641–649 (2001)CrossRefGoogle Scholar
  22. 22.
    F. Vaisman, P.H. Rosado de Castro, F.P. Lopes, D.B. Kendler, C.H. Pessoa, D.A. Bulzico et al. Is there a role for peptide receptor radionuclide therapy in medullary thyroid cancer? Clin. Nucl. Med. 40, 123–127 (2015)CrossRefGoogle Scholar
  23. 23.
    F. Iten, B. Muller, C. Schindler, C. Rochlitz, D. Oertli, H.R. Macke et al. Response to [90Yttrium-DOTA]-TOC treatment is associated with long-term survival benefit in metastasized medullary thyroid cancer: a phase II clinical trial. Clin. Cancer Res. 13, 6696–6702 (2007)CrossRefGoogle Scholar
  24. 24.
    B. Nilica, D. Waitz, V. Stevanovic, C. Uprimny, D. Kendler, S. Buxbaum et al. Direct comparison of (68)Ga-DOTA-TOC and (18)F-FDG PET/CT in the follow-up of patients with neuroendocrine tumour treated with the first full peptide receptor radionuclide therapy cycle. Eur. J. Nucl. Med. Mol. Imaging 43, 1585–1592 (2016)CrossRefGoogle Scholar
  25. 25.
    J.A. Meijer, S. le Cessie, W.B. van den Hout, J. Kievit, J.W. Schoones, J.A. Romijn et al. Calcitonin and carcinoembryonic antigen doubling times as prognostic factors in medullary thyroid carcinoma: a structured meta-analysis. Clin. Endocrinol. (Oxf.). 72, 534–542 (2010)CrossRefGoogle Scholar
  26. 26.
    H.H. Verbeek, J.T. Plukker, K.P. Koopmans, J.W. de Groot, R.M. Hofstra, A.C. Muller Kobold et al. Clinical relevance of 18F-FDG PET and 18F-DOPA PET in recurrent medullary thyroid carcinoma. J. Nucl. Med. 53, 1863–1871 (2012)CrossRefGoogle Scholar
  27. 27.
    T.V. Bogsrud, D. Karantanis, M.A. Nathan, B.P. Mullan, G.A. Wiseman, J.L. Kasperbauer et al. The prognostic value of 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography in patients with suspected residual or recurrent medullary thyroid carcinoma. Mol. Imaging Biol.: MIB 12, 547–553 (2010)CrossRefGoogle Scholar
  28. 28.
    A.L. Giraudet, D. Vanel, S. Leboulleux, A. Auperin, C. Dromain, L. Chami et al. Imaging medullary thyroid carcinoma with persistent elevated calcitonin levels. J. Clin. Endocrinol. Metab. 92, 4185–4190 (2007)CrossRefGoogle Scholar
  29. 29.
    L.Y.I. Yamaga, M.L. Cunha, G.C. Campos Neto, M.R.T. Garcia, J.H. Yang, C.P. Camacho et al. 68Ga-DOTATATE PET/CT in recurrent medullary thyroid carcinoma: a lesion-by-lesion comparison with (111)In-octreotide SPECT/CT and conventional imaging. Eur. J. Nucl. Med. Mol. Imaging 44, 1695–1701 (2017)CrossRefGoogle Scholar
  30. 30.
    A.R. Romero-Lluch, J.I. Cuenca-Cuenca, R. Guerrero-Vazquez, A.J. Martinez-Ortega, J.L. Tirado-Hospital, I. Borrego-Dorado et al. Diagnostic utility of PET/CT with (18)F-DOPA and (18)F-FDG in persistent or recurrent medullary thyroid carcinoma: the importance of calcitonin and carcinoembryonic antigen cutoff. Eur. J. Nucl. Med. Mol. Imaging 44, 2004–2013 (2017)CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Endocrinology, Diabetes and MetabolismCentro Hospitalar São JoãoPortoPortugal
  2. 2.Faculty of Medicine of University of PortoPortoPortugal
  3. 3.Instituto de Investigação e Inovação em SaúdeUniversity of PortoPortoPortugal
  4. 4.Nuclear Medicine DepartmentCentro Hospitalar do PortoPortoPortugal
  5. 5.Nuclear Medicine DepartmentInstituto Português de Oncologia do PortoPortoPortugal
  6. 6.Department of EndocrinologyInstituto Português de Oncologia do PortoPortoPortugal
  7. 7.Medical Physics, Radiobiology and Radiological Protection GroupCentro de Investigação do IPO-PortoPortoPortugal

Personalised recommendations