Abstract
Purpose
This study sought to evaluate and compare the utility of 18-F-fluorodihydroxyphenylalanine (18F-DOPA) and 18-F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) for identification of lesions in patients with recurrent medullary thyroid carcinoma (MTC). In addition, we analyzed the correlation between the calcitonin (Ct), carcinoembryonic antigen (CEA) levels, each doubling time (DT), and PET positivity. We evaluated the reliability of the 150 pg/mL Ct cutoff set by the American Thyroid Association guidelines for further imaging (including 18F-DOPA PET/CT).
Methods
We prospectively recruited 18 patients with recurrent MTC, identified by elevation of Ct or CEA. Each patient underwent a 18F-FDG PET/CT and a 18F-DOPA PET/CT.
Results
Abnormal uptakes were detected with 18F-DOPA (n=12) and 18F-FDG (n=9), (sensitivity of 66.7% vs. 50%; p<0.01). Twenty-eight lesions were detected with 18F-DOPA vs. 16 lesions with 18F-FDG (1.56±1.5 vs. 0.89±1.18 lesions per patient; p=0.01). None of our patients showed additional lesions with 18F-FDG in comparison to 18F-DOPA. Patient-based detection rate increased significantly with Ct levels ≥150 pg/mL vs. Ct<150 pg/mL for both 18F-DOPA (sensitivity 90.9% vs. 28.6%; p=0.013) and 18F-FDG PET/CT (sensitivity 72.7% vs. 14.3%; p=0.025). Using a CEA cutoff of ≥5 ng/mL, detection rates of 18F-DOPA and 18F-FDG PET/CT were 81.1% and 72.7%, respectively. No correlation between Ct-DT or CEA-DT and PET positivity was found. Histological confirmation was obtained in eight patients.
Conclusions
18F-DOPA PET/CT appears to be superior to 18F-FDG PET/CT in detecting and locating lesions in patients with recurrent MTC. This technique tends to be especially useful in patients with negative results in other imaging modalities and Ct≥150 pg/mL or CEA≥5 ng/mL.
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References
Wells SA Jr, Asa SL, Dralle H, Elisei R, Evans DB, Gagel RF, et al. Revised american thyroid association guidelines for the management of medullary thyroid carcinoma. Thyroid. 2015;25(6):567–610. doi:10.1089/thy.2014.0335.
Hu MI, Ying AK, Jimenez C. Update on medullary thyroid cancer. Endocrinol Metab Clin North Am. 2014;43(2):423–42. doi:10.1016/j.ecl.2014.02.004.
Balogova S, Talbot JN, Nataf V, Michaud L, Huchet V, Kerrou K, et al. 18F-fluorodihydroxyphenylalanine vs other radiopharmaceuticals for imaging neuroendocrine tumours according to their type. Eur J Nucl Med Mol Imaging. 2013;40(6):943–66. doi:10.1007/s00259-013-2342-x.
Minn H, Kauhanen S, Seppänen M, Nuutila P. 18F-FDOPA: a multiple-target molecule. J Nucl Med. 2009;50(12):1915–8. doi:10.2967/jnumed.109.065664.
Hoegerle S, Altehofer C, Ghanem N, Brink I, Moser E, Nitzsche E. 18F-DOPA positron emission tomography for tumour detection in patients with medullary thyroid carcinoma and elevated calcitonin levels. Eur J Nucl Med. 2001;28:64–71.
Beuthien-Baumann B, Strumpf A, Zessin J, Bredow J, Kotzerke J. Diagnostic impact of PET with 18F-FDG, 18F-DOPA and 3-Omethyl- 6-[18F]fluoro-DOPA in recurrent or metastatic medullary thyroid carcinoma. Eur J Nucl Med Mol Imaging. 2007;34(10):1604–9.
Koopmans KP, de Groot JWB, Plukke JTM, de Vries EG, Kema IP, Sluiter WJ, et al. 18F-dihydroxyphenylalanine PET in patients with biochemical evidence of medullary thyroid cancer: relation to tumor differentiation. J Nucl Med. 2008;49:524–31. doi:10.2967/jnumed.107.047720.
Beheshti M, Pöcher S, Vali R, Waldenberger P, Broinger G, Nader M, et al. The value of 18F-DOPA PET-CT in patients with medullary thyroid carcinoma: comparison with 18F-FDG PETCT. Eur Radiol. 2009;19:1425–34. doi:10.1007/s00330-008-1280-7.
Luster M, Karges W, Zeich K, Pauls S, Verburg FA, Dralle H, et al. Clinical value of 18-fluorine-fluorodihydroxyphenylalanine positron emission tomography/computed tomography in the follow-up of medullary thyroid carcinoma. Thyroid. 2010;20(5):527–33. doi:10.1089/thy.2009.0342.
Marzola MC, Pelizzo MR, Ferdeghini M, Toniato A, Massaro A, Ambrosini V, et al. Dual PET/CT with (18)F-DOPA and (18)FFDG in metastatic medullary thyroid carcinoma and rapidly increasing calcitonin levels: comparison with conventional imaging. Eur J Surg Oncol. 2010;36(4):414–21. doi:10.1016/j.ejso.2010.01.001.
Kauhanen S, Schalin-Jäntti C, Seppänen M, Kajander S, Virtanen S, Schildt J, et al. Complementary roles of 18F-DOPA PET/CT and 18F-FDG PET/CT in medullary thyroid cancer. J Nucl Med. 2011;52(12):1855–63. doi:10.2967/jnumed.111.094771.
Treglia G, Castaldi P, Villani MF, Perotti G. deWaure C, Filice A, et al. Comparison of 18F-DOPA, 18F-FDG and 68Gasomatostatin analogue PET/CT in patients with recurrent medullary thyroid carcinoma. Eur J Nucl Med Mol Imaging. 2012;39(4):569–80. doi:10.1007/s00259-011-2031-6.
Verbeek HH, Plukker JT, Koopmans KP, de Groot JW, Hofstra RM, Muller Kobold AC, et al. Clinical relevance of 18F-FDG PET and 18F-DOPA PET in recurrent medullary thyroid carcinoma. J Nucl Med. 2012;53(12):1863–71. doi:10.2967/jnumed.112.105940.
Sesti A, Mayerhoefer M, Weber M, Anner P, Wadsak W, Dudczak R, et al. Relevance of calcitonin cut-off in the follow-up of medullary thyroid carcinoma for conventional imaging and 18-fluorine-fluorodihydroxyphenylalanine PET. Anticancer Res. 2014;34(11):6647–54.
Treglia G, Cocciolillo F, Di Nardo F, Poscia A, de Waure C, Giordano A, et al. Detection rate of recurrent medullary thyroid carcinoma using fluorine-18 dihydroxyphenylalanine positron emission tomography: a meta-analysis. Acad Radiol. 2012;19(10):1290–9. doi:10.1016/j.acra.2012.05.008.
Kloos RT, Eng C, Evans DB, Francis GL, Gagel RF, Gharib H, et al. Medullary thyroid cancer: management guidelines of the American Thyroid Association. Thyroid. 2009;19(6):565–612. doi:10.1089/thy.2008.0403.
Boellaard R, O’Doherty MJ, Weber WA, Mottaghy FM, Lonsdale MN, Stroobants SG, et al. FDG PET and PET/CT: EANM procedure guidelines for tumour PET imaging: version 1.0. Eur J Nucl Med Mol Imaging. 2010;37(1):181–200. doi:10.1007/s00259-009-1297-4.
Perros P, Boelaert K, Colley S, Evans C, Evans RM, Gerrard Ba G, et al. Guidelines for the management of thyroid cancer. Clin Endocrinol (Oxf). 2014;81(Suppl 1):1–122. doi:10.1111/cen.12515.
Schlumberger M, Bastholt L, Dralle H, Jarzab B, Pacini F, Smit JW, et al. European thyroid association guidelines for metastatic medullary thyroid cancer. Eur Thyroid J. 2012;1(1):5–14. doi:10.1159/000336977.
Leenhardt L, Erdogan MF, Hegedus L, Mandel SJ, Paschke R, Rago T, et al. 2013 European thyroid association guidelines for cervical ultrasound scan and ultrasound-guided techniques in the postoperative management of patients with thyroid cancer. Eur Thyroid J. 2013;2(3):147–59. doi:10.1159/000354537.
Minn H, Kemppainen J, Kauhanen S, Forsback S, Seppänen M. 18F-fluorodihydroxyphenylalanine in the diagnosis of neuroendocrine tumors. PET Clin. 2014;9(1):27–36. doi:10.1016/j.cpet.2013.08.013.
Archier A, Heimburger C, Guerin C, Morange I, Palazzo FF, Henry JF, et al. 18F-DOPA PET/CT in the diagnosis and localization of persistent medullary thyroid carcinoma. Eur J Nucl Med Mol Imaging. 2016;43(6):1027–33. doi:10.1007/s00259-015-3227-y.
Aziz AL, Dierickx L, Courbon F, Taïeb D, Zerdoud S. (18)F-Fluorine-18-l-dihydroxyphenylalanine ((18)F-DOPA) positive isolated peritoneal carcinomatosis from a MENII-related medullary thyroid carcinoma. About an atypical metastatic site and utility of (18)F-FDOPA. Clin Case Rep. 2015;3(2):81–3. doi:10.1002/ccr3.159.
Ruiz JB, Orré M, Cazeau AL. Henriques de Figueiredo B, Godbert Y. 18F-DOPA PET/CT in Orbital Metastasis From Medullary Thyroid Carcinoma. Clin Nucl Med. 2016;41(6):e296–7. doi:10.1097/RLU.0000000000001216.
Treglia G, Rufini V, Salvatori M, Giordano A, Giovanella L. PET Imaging in Recurrent Medullary Thyroid Carcinoma. Int J Mol Imaging. 2012;2012:324686. doi:10.1155/2012/324686.
Skoura E. Despicting medullary thyroid cancer recurrence: the past and the future of nuclear medicine imaging. Int J Endocrinol Metab. 2013;11(4):e8156. doi:10.5812/ijem.8156.
Conry BG, Papathanasiou ND, Prakash V, Kayani I, Caplin M, Mahmood S, 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. 2010;37:49–57. doi:10.1007/s00259-009-1204-z.
Ozkan ZG, Kuyumcu S, Uzum AK, Gecer MF, Ozel S, Aral F, et al. Comparison of 68Ga-DOTATATE PET-CT, 18F-FDG PET-CT and 99mTc-(V)DMSA scintigraphy in the detection of recurrent or metastatic medullary thyroid carcinoma. Nucl Med Commun. 2015;36(3):242–50. doi:10.1097/MNM.0000000000000240.
Tran K, Khan S, Taghizadehasl M, Palazzo F, Frilling A, Todd JF, et al. Gallium-68 Dotatate PET/CT is superior to other imaging modalities in the detection of medullary carcinoma of the thyroid in the presence of high serum calcitonin. Hell J Nucl Med. 2015;18(1):19–24. doi:10.1967/s002449910163.
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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
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Romero-Lluch, A.R., Cuenca-Cuenca, J.I., Guerrero-Vázquez, R. et al. Diagnostic utility of PET/CT with 18F-DOPA and 18F-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). https://doi.org/10.1007/s00259-017-3759-4
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DOI: https://doi.org/10.1007/s00259-017-3759-4