Prospective evaluation of 68Ga-DOTANOC PET-CT in differentiated thyroid cancer patients with raised thyroglobulin and negative 131I-whole body scan: comparison with 18F-FDG PET-CT

  • Parveen Kundu
  • Sneh Lata
  • Punit Sharma
  • Harmandeep Singh
  • Arun Malhotra
  • Chandrasekhar BalEmail author
Original Article



The purpose of the study was to evaluate the role of 68Ga-DOTANOC PET-CT in differentiated thyroid cancer (DTC) patients with negative 131I-whole body scan (WBS) along with serially increasing serum thyroglobulin (Tg), and compare the same with 18F-FDG PET-CT.


Sixty two DTC patients with serially rising Tg levels and negative 131I-WBS were prospectively enrolled. All patients underwent 68Ga-DOTANOC PET-CT and 18F-FDG PET-CT within an interval of two weeks. PET-CT analysis was done on a per-patient basis, location wise and lesion wise. All PET-CT lesions were divided into four categories-local, nodal, pulmonary and skeletal. Histopathology and/or serial serum Tg level, clinical and imaging follow up (minimum-1 year) were used as a reference standard.


Ga-DOTANOC PET-CT demonstrated disease in 40/62 (65 %) patients and 18F-FDG PET-CT in 45/62 (72 %) patients, with no significant difference on McNemar analysis (p = 0.226). Per-patient sensitivity and specificity of 68Ga-DOTANOC PET-CT was 78.4 %, 100 %, and for 18F-FDG PET-CT was 86.3 %, 90.9 %, respectively. Out of 186 lesions detected by both PET-CTs, 121/186 (65 %) lesions were seen on 68Ga-DOTANOC PET-CT and 168/186 (90.3 %) lesions on 18F-FDG PET-CT (p < 0.0001). There were 103/186 (55 %) lesions concordant on both. Excellent agreement was noted between 68Ga-DOTANOC PET-CT and 18F-FDG PET-CT for detection of local disease (ĸ = 0.92), while moderate agreement was noted for nodal and pulmonary disease (ĸ = 0.67). 68Ga-DOTANOC PET-CT changed management in 21/62 (34 %) patients and 18F-FDG PET-CT in 17/62 (27 %) patients.


Ga-DOTANOC PET-CT is inferior to 18F-FDG PET-CT on lesion based but not on patient based analysis for detection of recurrent/residual disease in DTC patients with negative WBS scan and elevated serum Tg levels. It can also help in selection of potential candidates for peptide receptor radionuclide therapy.


Dedifferentiated thyroid cancer PET-CT 68Ga-DOTANOC 18F-FDG 


Conflict of interest

The authors declare that there is no conflict of interest.

No funding was received from any organization for this study.


  1. 1.
    Menendez Torre E, Lopez Carballo MT, Rodriguez Erdozain RM, et al. Prognostic value of thyroglobulin serum levels and 131I whole-body scan after initial treatment of low-risk differentiated thyroid cancer. Thyroid. 2004;14:301–6.PubMedCrossRefGoogle Scholar
  2. 2.
    Preissner CM, O’Kane DJ, Singh RJ, et al. Phantoms in the assay tube:heterophile antibody interference in serum thyroglobulin assays. J Clin Endocrinol Metab. 2003;88:3069–74.PubMedCrossRefGoogle Scholar
  3. 3.
    Ma C, Kuang A, Xie J, Ma T. Possible explanations for patients with discordant findings of serum thyroglobulin and 131I whole-body scanning. J Nucl Med. 2005;46:1473–80.PubMedGoogle Scholar
  4. 4.
    Knauf JA, Ma X, Smith EP, et al. Targeted expression of BRAFV600E in thyroid cells of transgenic mice results in papillary thyroid cancers that undergo dedifferentiation. Cancer Res. 2005;65:4238–45.PubMedCrossRefGoogle Scholar
  5. 5.
    Xing M. Gene methylation in thyroid tumorigenesis. Endocrinology. 2007;148:948–53.PubMedCrossRefGoogle Scholar
  6. 6.
    Min JJ, Chung JK, Lee YJ, et al. Relationship between expression of the sodium/iodide symporter and 131I uptake in recurrent lesions of differentiated thyroid carcinoma. Eur J Nucl Med. 2001;28:639–45.CrossRefGoogle Scholar
  7. 7.
    Krishna L, Dadparvar S, Brady LW, et al. Paradoxical changes in iodine-131 scintigraphic findings in advanced follicular thyroid cancer. J Nucl Med. 1993;34:1574–6.PubMedGoogle Scholar
  8. 8.
    Grunwald F, Kalicke T, Feine U, et al. Fluorine-18 fluorodeoxyglucose positron emission tomography in thyroid cancer: results of a multicentre study. Eur J Nucl Med. 1999;26:1547–52.PubMedCrossRefGoogle Scholar
  9. 9.
    Luong QT, O’Kelly J, Braunstein GD, et al. Antitumor activity of suberoylanilidehydroxamic acid against thyroid cancer cell lines in vitro and in vivo. Clin Cancer Res. 2006;12:5570–7.PubMedCrossRefGoogle Scholar
  10. 10.
    Catalano MG, Fortunati N, Pugliese M, et al. Valproic acid induces apoptosis and cell cycle arrest in poorly differentiated thyroid cancer cells. J Clin Endocrinol Metab. 2005;90:1383–9.PubMedCrossRefGoogle Scholar
  11. 11.
    Kurebayashi J, Tanaka K, Otsuki T, et al. All-trans-retinoic acid modulates expression levels of thyroglobulin and cytokines in a human poorly differentiated papillary thyroid carcinoma cell line, KTC-1. J Clin Endocrinol Metab. 2000;85:2889–96.PubMedGoogle Scholar
  12. 12.
    Teunissen JJ, Kwekkeboom DJ, Kooij PP, Bakker WH, Krenning EP. Peptide receptor radionuclide therapy for non-radioiodine-avid differentiated thyroid carcinoma. J Nucl Med. 2005;46:107S–14.PubMedGoogle Scholar
  13. 13.
    Klagge A, Krause K, Schierle K, Steinert F, Dralle H, Fuhrer D. Somatostatin receptor subtype expression in human thyroid tumours. Horm Metab Res. 2010;42:237–40.PubMedCrossRefGoogle Scholar
  14. 14.
    Pisarek H, Stepien T, Kubiak R, Borkowska E, Pawlikowski M. Expression of somatostatin receptor subtypes in human thyroid tumors: the immunohistochemical and molecular biology (RT-PCR) investigation. Thyroid Res. 2009;2:1–8.PubMedCentralPubMedCrossRefGoogle Scholar
  15. 15.
    Sancak S, Hardt A, Singer J, et al. Somatostatin receptor 2 expression determined by immunohistochemistry in cold thyroid nodules exceeds that of hot thyroid nodules, papillary thyroid carcinoma, and Graves’ disease. Thyroid. 2010;20:505–11.PubMedCrossRefGoogle Scholar
  16. 16.
    Pazaitou-Panayiotou K, Janson ET, Koletsa T, et al. Somatostatin receptor expression in non-medullary thyroid carcinomas. Hormones. 2012;11:290–6.PubMedCrossRefGoogle Scholar
  17. 17.
    Baudin E, Schlumberger M, Lumbroso J, Travagli JP, Caillou B, Parmentier C. Octreotide scintigraphy in patients with differentiated thyroid carcinoma: contribution for patients with negative radioiodine scan. J Clin Endocrinol Metab. 1996;81:2541–4.PubMedGoogle Scholar
  18. 18.
    Giammarile F, Houzard C, Bournaud C, Hafdi Z, Sassolas G, Borson-Chazot F. Diagnostic management of suspected metastatic thyroid carcinoma: clinical value of octreotide scintigraphy in patients with negative high-dose radioiodine scans. Eur J Endocrinol. 2004;150:277–83.PubMedCrossRefGoogle Scholar
  19. 19.
    Stokkel MP, Verkooijen RB, Smit JW. Indium-111 octreotide scintigraphy for the detection of non-functioning metastases from differentiated thyroid cancer: diagnostic and prognostic value. Eur J Nucl Med Mol Imaging. 2004;31:950–7.PubMedCrossRefGoogle Scholar
  20. 20.
    Antunes P, Ginj M, Zhang H, et al. Are radiogallium-labelled DOTA-conjugated somatostatin analogues superior to those labelled with other radiometals? Eur J Nucl Med Mol Imaging. 2007;34:982–93.PubMedCrossRefGoogle Scholar
  21. 21.
    Wild D, Schmitt JS, Ginj M, et al. DOTA-NOC, a high affiniy ligand of somatostatin receptor subtypes 2, 3 and 5 for labelling with various radiometals. Eur J Nucl Med Mol Imaging. 2003;30:1338–47.PubMedCrossRefGoogle Scholar
  22. 22.
    Zhernosekov KP, Filosofov DV, Baum RP, et al. Processing of generator-produced 68Ga for medical application. J Nucl Med. 2007;48:1741–8.PubMedCrossRefGoogle Scholar
  23. 23.
    Middendorp M, Selkinski I, Happel C, Kranert WT, Grünwald F. Comparison of positron emission tomography with [(18)F]FDG and [(68)Ga]DOTATOC in recurrent differentiated thyroid cancer: preliminary data. Q J Nucl Med Mol Imaging. 2010;54:76–83.PubMedGoogle Scholar
  24. 24.
    Kowalski J, Henze M, Schuhmacher J, Maecke HR, Hofmann M, Haberkorn U. Evaluation of positron emission tomography imaging using [68Ga]-DOTA-D-Phe1-Tyr3-octreotide in comparison to [111In]-DTPAOC SPECT. First results in patients with neuroendocrine tumors. Mol Imaging Biol. 2003;5:42–8.PubMedCrossRefGoogle Scholar
  25. 25.
    Buchmann I, Henze M, Engelbrecht S, et al. Comparison of 68Ga-DOTATOC PET and 111In-DTPAOC (Octreoscan) SPECT in patients with neuroendocrine tumours. Eur J Nucl Med Mol Imaging. 2007;34:1617–26.PubMedCrossRefGoogle Scholar
  26. 26.
    Finkelstein SE, Grigsby PW, Siegel BA, Dehdashti F, Moley JF, Hall BL. Combined [18F]Fluorodeoxyglucose positron emission tomography and computed tomography (FDG-PET/CT) for detection of recurrent, 131I-negative thyroid cancer. Ann Surg Oncol. 2008;15:286–92.PubMedCrossRefGoogle Scholar
  27. 27.
    Dong M, Liu Z, Zhao K, et al. Value of 18F-FDG-PET/PET-CT in differentiated thyroid carcinoma with radioiodine-negative whole-body scan: a meta-analysis. Nucl Med Commun. 2009;30:639–50.PubMedCrossRefGoogle Scholar
  28. 28.
    Gabriel M, Froehlich F, Decristoforo C, et al. 99mTc-EDDA/HYNIC-TOC and (18)F-FDG in thyroid cancer patients with negative (131)I whole-body scans. Eur J Nucl Med Mol Imaging. 2004;31:330–41.PubMedCrossRefGoogle Scholar
  29. 29.
    Rodrigues M, Traub-Weidinger T, Leimer M, et al. Value of 111In-DOTA-lanreotide and 111In-DOTA-DPhe1-Tyr3-octreotide in differentiated thyroid cancer: results of in vitro binding studies and in vivo comparison with 18F-FDG PET. Eur J Nucl Med Mol Imaging. 2005;32:1144–51.PubMedCrossRefGoogle Scholar
  30. 30.
    Rodrigues M, Li S, Gabriel M, Heute D, Greifeneder M, Virgolini I. 99mTc-depreotide scintigraphy versus 18F-FDG-PET in the diagnosis of radioiodine-negative thyroid cancer. J Clin Endocrinol Metab. 2006;91:3997–4000.PubMedCrossRefGoogle Scholar
  31. 31.
    Naswa N, Sharma P, Kumar A, Nazar AH, Kumar R, Chumber S, et al. Gallium-68-DOTA-NOC PET/CT of patients with gastroenteropancreatic neuroendocrine tumors: a prospective single-center study. AJR Am J Roentgenol. 2011;197:1221–38.PubMedCrossRefGoogle Scholar
  32. 32.
    Basu S, Abhyankar A, Kand P, Kumar R, Asopa R, Rajan MG, et al. Reverse discordance' between 68Ga-DOTA-NOC PET/CT and 177Lu-DOTA-TATE posttherapy scan: the plausible explanations and its implications for high-dose therapy with radiolabeled somatostatin receptor analogs. Nucl Med Commun. 2011;32:654–8.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Parveen Kundu
    • 1
  • Sneh Lata
    • 1
  • Punit Sharma
    • 1
  • Harmandeep Singh
    • 1
  • Arun Malhotra
    • 1
  • Chandrasekhar Bal
    • 1
    Email author
  1. 1.Department of Nuclear MedicineAll India Institute of Medical SciencesAnsari NagarIndia

Personalised recommendations