Skip to main content

Advertisement

SpringerLink
Log in

Molecular imaging and related therapeutic options for medullary thyroid carcinoma: state of the art and future opportunities

  • Published:
Reviews in Endocrine and Metabolic Disorders Aims and scope Submit manuscript

Abstract

Due to its rarity and non-specific clinical presentation, accurate diagnosis, and optimal therapeutic strategy of medullary thyroid carcinoma (MTC) remain challenging. Molecular imaging provides valuable tools for early disease detection, monitoring treatment response, and guiding personalized therapies. By enabling the visualization of molecular and cellular processes, these techniques contribute to a deeper understanding of disease mechanisms and the development of more effective clinical interventions. Different nuclear imaging techniques have been studied for assessing MTC, and among them, PET/CT utilizing multiple radiotracers has emerged as the most effective imaging method in clinical practice. This review aims to provide a comprehensive summary of the current use of advanced molecular imaging modalities, with a particular focus on PET/CT, for the management of patients with MTC. It aims to guide physicians towards a rationale for the use of molecular imaging also including theranostic approaches and novel therapeutical opportunities. Overall, we emphasize the evolving role of nuclear medicine in MTC. The integration of diagnostics and therapeutics by in vivo molecular imaging represents a major opportunity to personalize treatment for individual patients, with targeted radionuclide therapy being one representative example.

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
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Hazard JB, Hawk WA, Crile G. Medullary (solid) carcinoma of the thyroid; a clinicopathologic entity. J Clin Endocrinol Metab. 1959;19:152–61.

    Article  CAS  PubMed  Google Scholar 

  2. Costante G, Meringolo D, Durante C, Bianchi D, Nocera M, Tumino S, Crocetti U, Attard M, Maranghi M, Torlontano M, Filetti S. Predictive value of serum calcitonin levels for preoperative diagnosis of medullary thyroid carcinoma in a cohort of 5817 consecutive patients with thyroid nodules. J Clin Endocrinol Metab. 2007;92:450–5.

    Article  CAS  PubMed  Google Scholar 

  3. Essig GF Jr, Porter K, Schneider D, Arpaia D, Lindsey SC, Busonero G, Fineberg D, Fruci B, Boelaert K, Smit JW, Meijer JA, Duntas LH, Sharma N, Costante G, Filetti S, Sippel RS, Biondi B, Topliss DJ, Pacini F, Maciel RM, Walz PC, Kloos RT. Thyroid. 2016;26:1563–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Trimboli P, Mian C, Piccardo A, Treglia G. Diagnostic tests for medullary thyroid carcinoma: an umbrella review. Endocrine. 2023;6 (ahead of print).

  5. Scheuba C, Kaserer K, Moritz A, Drosten R, Vierhapper H, Bieglmayer C, Haas OA, Niederle B. Endocr Relat Cancer. 2009;16:243–53.

    Article  CAS  PubMed  Google Scholar 

  6. Machens A, Dralle H. Biological relevance of medullary thyroid microcarcinoma. J Clin Endocrinol Metab. 2012;97:1547–53.

    Article  CAS  PubMed  Google Scholar 

  7. Takahashi M, Ritz J, Cooper GM. Activation of a novel human transforming gene, ret, by DNA rearrangement. Cell. 1995;42:581–8.

    Article  Google Scholar 

  8. Falchetti A, Marini F, Luzi E, Tonelli F, Brandi ML. Multiple endocrine neoplasms. Best Pract Res Clin Rheumatol. 2008;22:149–63.

    Article  CAS  PubMed  Google Scholar 

  9. Eng C, Clayton D, Schuffenecker I, Lenoir G, Cote G, Gagel RF, van Amstel HK, Lips CJ, Nishisho I, Takai SI, Marsh DJ, Robinson BG, Frank-Raue K, Raue F, Xue F, Noll WW, Romei C, Pacini F, Fink M, Niederle B, Zedenius J, Nordenskjold M, Komminoth P, Hendy GN, Mulligan LM, et al. The relationship between specific RET proto-oncogene mutations and disease phenotype in multiple endocrine neoplasia type 2. International RET mutation consortium analysis. JAMA. 1996;276:1575–9.

    Article  CAS  PubMed  Google Scholar 

  10. Moley JF. (2010) Medullary thyroid carcinoma: Management of lymph node metastases. J Natl Compr Canc Netw. 2010;8:549–556.

  11. Wells SA, Asa SL, Dralle H, Elisei R, Evans DB, Gagel RF, Lee N, Machens A, Moley JF, Pacini F, Raue F, Frank-Raue K, Robinson B, Rosenthal MS, Santoro M, Schlumberger M, Shah M, Waguespack SG, The American Thyroid Association Guidelines Task Force on Medullary Thyroid Carcinoma. Revised american thyroid Association guidelines for the management of medullary thyroid carcinoma. Thyroid. 2015;25:567–610.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Pazaitou-Panayiotou K, Chrisoulidou A, Mandanas S, Tziomalos K, Doumala E, Patakiouta F. Predictive factors that influence the course of medullary thyroid carcinoma. Int J Clin Oncol. 2014;19:445–51.

    Article  PubMed  Google Scholar 

  13. Mehrotra PK, Mishra A, Mishra SK, Agarwal G, Agarwal A, Verma AK. Medullary thyroid Cancer: clinico-pathological Profile and Outcome in a Tertiary Care Center in North India. World J Surg. 2011;35:1273–80.

    Article  PubMed  Google Scholar 

  14. Hadoux J, Pacini F, Tuttle RM, Schlumberger M. Management of advanced medullary thyroid cancer. Lancet Diabetes Endocrinol. 2016;4:64–71.

    Article  CAS  PubMed  Google Scholar 

  15. Elisei R, Schlumberger MJ, Müller SP, Schöffski P, Brose MS, Shah MH, et al. Cabozantinib in progressive medullary thyroid cancer. J Clin Oncol. 2013;31:3639–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Wells SA, Robinson BG, Gagel RF, Dralle H, Fagin JA, Santoro M, et al. Vandetanib in patients with locally advanced or metastatic medullary thyroid cancer: a randomized, double-blind phase III trial. J Clin Oncol. 2012;30:134–41.

    Article  CAS  PubMed  Google Scholar 

  17. Schlumberger M, Elisei R, Müller S, Schöffski P, Brose M, Shah M, et al. Overall survival analysis of EXAM, a phase III trial of cabozantinib in patients with radiographically progressive medullary thyroid carcinoma. Ann Oncol. 2017;28:2813–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Ciampi R, Romei C, Ramone T, Prete A, Tacito A, Cappagli V, et al. Genetic Landscape of somatic mutations in a large cohort of sporadic medullary thyroid Carcinomas studied by next-generation targeted sequencing. iScience. 2019;20:324–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Subbiah V, Hu MI, Wirth LJ, Schuler M, Mansfield AS, Curigliano G, et al. Pralsetinib for patients with advanced or metastatic RET-altered thyroid cancer (ARROW): a multi-cohort, open-label, registrational, phase 1/2 study. Lancet Diabetes Endocrinol. 2021;9:491–501.

    Article  CAS  PubMed  Google Scholar 

  20. 10, Wirth LJ, Sherman E, Robinson B, Solomon B, Kang H, Lorch J, et al. Efficacy of Selpercatinib in RET-Altered thyroid cancers. N Engl J Med. 2020;383:825–35.

    Article  Google Scholar 

  21. Schlumberger M, Abdelmoumene N, Delisle MJ, Couette JE. Treatment of advanced medullary thyroid cancer with an alternating combination of 5 FU-streptozocin and 5 FU-dacarbazine. The Groupe d’Etude des Tumeurs a calcitonine (GETC). Br J Cancer. 1995;71:363–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Wang L, Kou H, Chen W, Lu M, Zhou L, Zou C. The diagnostic value of Ultrasound in Medullary thyroid carcinoma: a comparison with computed tomography. Technol Cancer Res Treat. 2020;19:153303382090583.

    Article  Google Scholar 

  23. Liu MJ, Liu ZF, Hou YY, Men YM, Zhang YX, Gao LY, Liu H. Ultrasonographic characteristics of medullary thyroid carcinoma: a comparison with papillary thyroid carcinoma. Oncotarget. 2017;8:27520–8.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Lai X, Liu M, Xia Y, Wang L, Bi Y, Li X, Zhang B, Yang M, Dai Q, Jiang Y. Hypervascularity is more frequent in medullary thyroid carcinoma: compared with papillary thyroid carcinoma. Medicine. 2016;95:e5502.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Valderrabano P, Klippenstein DL, Tourtelot JB, Ma Z, Thompson ZJ, Lilienfeld HS, McIver B. New american thyroid Association Sonographic patterns for thyroid nodules perform well in medullary thyroid carcinoma: institutional experience, systematic review, and Meta-Analysis. Thyroid. 2016;26:1093–100.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Ferrarazzo G, Camponovo C, Deandrea M, Piccardo A, Scappaticcio L, Trimboli P. Suboptimal accuracy of ultrasound and ultrasound-based risk stratification systems in detecting medullary thyroid carcinoma should not be overlooked. Findings from a systematic review with meta-analysis. Clin Endocrinol (Oxf). 2022;97:532–40.

    Article  PubMed  Google Scholar 

  27. Trimboli P, Castellana M, Piccardo A, Romanelli F, Grani G, Giovanella L, Durante C. The ultrasound risk stratification systems for thyroid nodule have been evaluated against papillary carcinoma. A meta-analysis. Rev Endocr Metab Disord. 2021;22:453–60.

    Article  PubMed  Google Scholar 

  28. Machens A, Dralle H. Biomarker-based risk stratification for previously untreated medullary thyroid Cancer. J Clin Endocrinol Metab. 2010;95:2655–63.

    Article  CAS  PubMed  Google Scholar 

  29. Klain M, Hadoux J, Nappi C, Finessi M, Ambrosio R, Schlumberger M, Cuocolo A, Deandreis D, Salvatore D. Imaging medullary thyroid cancer patients with detectable serum markers: state of the art and future perspectives. Endocrine. 2022;75:330–7.

    Article  CAS  PubMed  Google Scholar 

  30. Debnam JM, Guha-Thakurta N, Sun J, Wei W, Zafereo ME, Cabanillas ME, Buisson NM, Schellingerhout D. Distinguishing recurrent thyroid Cancer from residual nonmalignant thyroid tissue using multiphasic multidetector CT. AJNR Am J Neuroradiol. 2020;41:844–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Fitzgerald RT, Kuruva M, David R, Samant RS, Kumar M, Van Hemert R, Angtuaco EJ, Bodenner D, Stack BC Jr. Characterization of thyroid nodules by 4-Dimensional Computed Tomography: initial experience. J Comput Assist Tomogr. 2017;41:195–8.

    Article  PubMed  Google Scholar 

  32. Gürsoy Çoruh A, Uzun Ç, Kul M, Akkaya Z, Halil Elhan A, Gökcan K. The impact of arterial phase on the detection of cervical lymph node metastasis from papillary thyroid carcinoma: a quantitative evaluation on multiphasic computed tomography. J Comput Assist Tomogr. 2020;44:262–8.

    Article  PubMed  Google Scholar 

  33. Skinner MA, Moley JA, Dilley WG, Owzar K, Debenedetti MK, Wells SA Jr. Prophylactic thyroidectomy in multiple endocrine neoplasia type 2A. N Engl J Med. 2005;353:1105–13.

    Article  CAS  PubMed  Google Scholar 

  34. Giovanella L, Treglia G, Iakovou I, Mihailovic J, Verburg FA, Luster M. EANM practice guideline for PET/CT imaging in medullary thyroid carcinoma. Eur J Nucl Med Mol Imaging. 2020;47:61–77.

    Article  PubMed  Google Scholar 

  35. Castinetti F, Taïeb D. Positron emission tomography imaging in medullary thyroid carcinoma: time for reappraisal? Thyroid. 2021;31:151–5.

    Article  PubMed  Google Scholar 

  36. Treglia G, Sadeghi R, Giovinazzo F, Galiandro F, Annunziata S, Muoio B, Kroiss AS. PET with different radiopharmaceuticals in neuroendocrine neoplasms: an umbrella review of published meta-analyses. Cancers. 2021;13:5172.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Soussan M, Nataf V, Kerrou K, Grahek D, Pascal O, Talbot JN, Montravers F. Added value of early 18F-FDOPA PET/CT acquisition time in medullary thyroid cancer. Nucl Med Commun. 2012;33:775–9.

    Article  PubMed  Google Scholar 

  38. Fargette C, Imperiale A, Taïeb D. Molecular imaging of endocrine neoplasms with emphasis on 18F-DOPA PET: a practical approach for well-tailored imaging protocols. Q J Nucl Med Mol Imaging. 2022;66:141–7.

    Article  PubMed  Google Scholar 

  39. Rasul S, Hartenbach S, Rebhan K, Göllner A, Karanikas G, Mayerhoefer M, Mazal P, Hacker M, Hartenbach M. [18F]DOPA PET/ceCT in diagnosis and staging of primary medullary thyroid carcinoma prior to surgery. Eur J Nucl Med Mol Imaging. 2018;45:2159–69.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Filetti S, Durante C, Hartl D, Leboulleux S, Locati LD, Newbold K, Papotti MG, Berruti A. Guidelines Committee. Thyroid cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2019;30:1856–83.

    Article  CAS  PubMed  Google Scholar 

  41. Beheshti M, Pocher S, Vali R, Waldenberger P, Broinger G, Nader M, Kohlfurst S, Pirich C, Dralle H, Langsteger W. The value of 18F-DOPA PET-CT in patients with medullary thyroid carcinoma: comparison with 18F-FDG PET-CT. Eur Radiol. 2009;19:1425–34.

    Article  PubMed  Google Scholar 

  42. Brammen L, Niederle MB, Riss P, Scheuba C, Selberherr A, Karanikas G, Bodner G, Koperek O, Niederle B. Medullary thyroid carcinoma: do Ultrasonography and F-DOPA-PET-CT influence the initial Surgical Strategy? Ann Surg Oncol. 2018;25:3919–27.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Hoegerle S, Altehoefer 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.

    Article  CAS  PubMed  Google Scholar 

  44. Treglia G, Rufini V, Piccardo A, Imperiale A. Update on management of medullary thyroid carcinoma: focus on Nuclear Medicine. Semin Nucl Med. 2023 (Ahead of print).

  45. Beuthien-Baumann B, Strumpf A, Zessin J, Bredow J, Kotzerke J. Diagnostic impact of PET with 18F-FDG, 18F-DOPA and 3-O-methyl-6-[18F]fluoro-DOPA in recurrent or metastatic medullary thyroid carcinoma. Eur J Nucl Med Mol Imaging. 2007;34:1604–9.

    Article  CAS  PubMed  Google Scholar 

  46. Luster M, Karges W, Zeich K, Pauls S, Verburg FA, Dralle H, Glatting G, Buck AK, Solbach C, Neumaier B, Reske SN, Mottaghy FM. Clinical value of 18-fluorine-fluorodihydroxyphenylalanine positron emission tomography/computed tomography in the follow-up of medullary thyroid carcinoma. Thyroid. 2010;20:527–33.

    Article  CAS  PubMed  Google Scholar 

  47. Treglia G, Cocciolillo F, Di Nardo F, et al. Detection rate of recurrent medullary thyroid carcinoma using fluorine-18 dihydroxyphenylalanine positron emission tomography: a meta-analysis. Acad Radiol. 2012;19:1290–9.

    Article  PubMed  Google Scholar 

  48. Archier A, Heimburger C, Guerin C, Morange I, Palazzo FF, Henry JF, Schneegans O, Mundler O, Abdullah AE, Sebag F, Imperiale A, Taieb D. (18)F-DOPA PET/CT in the diagnosis and localization of persistent medullary thyroid carcinoma. Eur J Nucl Med Mol Imaging. 2016;43:1027–33.

    Article  CAS  PubMed  Google Scholar 

  49. Rotania M, Chabrier G, Imperiale A. Synchronous bilateral pheochromocytomas and bilobar medullary thyroid carcinoma revealed by 18F-FDOPA PET/CT in a MEN-2A asymptomatic patient. Endocrine. 2019;66:691–2.

    Article  CAS  PubMed  Google Scholar 

  50. Terroir M, Caramella C, Borget I, Bidault S, Dromain C, El Farsaoui K, Deandreis D, Grimaldi S, Lumbroso J, Berdelou A, Hadoux J, Hescot S, Hartl D, Baudin E, Schlumberger M, Leboulleux S. F-18-Dopa positron emission tomography/computed tomography is more sensitive than whole-body magnetic resonance imaging for the localization of persistent/recurrent disease of medullary thyroid cancer patients. Thyroid. 2019;29:1457–64.

    Article  CAS  PubMed  Google Scholar 

  51. Treglia G, Villani MF, Giordano A, Rufini V. Detection rate of recurrent medullary thyroid carcinoma using fluorine-18 fluorodeoxyglucose positron emission tomography: a meta-analysis. Endocrine. 2012;42:535–45.

    Article  CAS  PubMed  Google Scholar 

  52. Cheng X, Bao L, Xu Z, Li D, Wang J, Li Y. 18F-FDG-PET and 1-F-FDG-PET/CT in the detection of recurrent or metastatic medullary thyroid carcinoma: a systematic review and meta-analysis. J Med Imaging Radiat Oncol. 2012;56:136–42.

    Article  PubMed  Google Scholar 

  53. Caobelli F, Chiaravalloti A, Evangelista L, Saladini G, Schillaci O, Vadrucci M, Scalorbi F, Donner D, Alongi P, Young AIMN, Working Group. Predictive and prognostic value of 18F-DOPA PET/CT in patients affected by recurrent medullary carcinoma of the thyroid. Ann Nucl Med. 2018;32:7–15.

    Article  PubMed  Google Scholar 

  54. Kloos RT, Eng C, Evans DB, Francis GL, Gagel RF, Gharib H, Moley JF, Pacini F, Ringel MD, Schlumberger M, Wells SA Jr. ., and american thyroid Association Guidelines Task Force on Medullary thyroid carcinoma. Medullary thyroid cancer: management guidelines of the american thyroid Association. Thyroid. 2009;19:565–612.

    Article  PubMed  Google Scholar 

  55. Skoura E, Datseris IE, Rondogianni P, Tsagarakis S, Tzanela M, Skilakaki M, Exarhos D, Alevizaki M. Correlation between calcitonin levels and [(18)F]FDG-PET/CT in the detection of recurrence in patients with sporadic and Hereditary Medullary thyroid Cancer. ISRN Endocrinol. 2012;2012:375231.

    Article  PubMed  PubMed Central  Google Scholar 

  56. Giraudet AL, Vanel D, Leboulleux S, Auperin A, Dromain C, Chami L, Ny Tovo N, Lumbroso J, Lassau N, Bonniaud G, Hartl D, Travagli JP, Baudin E, Schlumberger M. Imaging medullary thyroid carcinoma with persistent elevated calcitonin levels. J Clin Endocrinol Metab. 2007;92:4185–90.

    Article  CAS  PubMed  Google Scholar 

  57. Treglia G, Goichot B, Giovanella L, Hindié E, Jha A, Pacak K, Taïeb D, Walter T, Imperiale A. Prognostic and predictive value of nuclear imaging in endocrine oncology. Endocrine. 2020;67:9–19.

    Article  CAS  PubMed  Google Scholar 

  58. Marzola MC, Pelizzo MR, Ferdeghini M, Toniato A, Massaro A, Ambrosini V, Fanti S, Gross MD, Al-Nahhas A, Rubello D. Dual PET/CT with (18)F-DOPA and (18)F-FDG in metastatic medullary thyroid carcinoma and rapidly increasing calcitonin levels: comparison with conventional imaging. Eur J Surg Oncol. 2010;36:414–21.

    Article  CAS  PubMed  Google Scholar 

  59. Salaun PY, Campion L, Ansquer C, Frampas E, Mathieu C, Robin P, Bournaud C, Vuillez JP, Taieb D, Rousseau C, Drui D, Mirallié E, Borson-Chazot F, Goldenberg DM, Chatal JF, Barbet J. Kraeber-Bodéré F. 18F-FDG PET predicts survival after pretargeted radioimmunotherapy in patients with progressive metastatic medullary thyroid carcinoma. Eur J Nucl Med Mol Imaging. 2014;41:1501–10.

    Article  CAS  PubMed  Google Scholar 

  60. Werner RA, Schmid JS, Higuchi T, Javadi MS, Rowe SP, Märkl B, Aulmann C, Fassnacht M, Kroiss M, Reiners C, Buck AK, Kreissl MC, Lapa C. Predictive value of FDG-PET in patients with advanced medullary thyroid carcinoma treated with vandetanib. J Nucl Med. 2018;59:756–61.

    Article  CAS  PubMed  Google Scholar 

  61. Werner RA, Bundschuh RA, Higuchi T, Javadi MS, Rowe SP, Zsótér N, Kroiss M, Fassnacht M, Buck AK, Kreissl MC, Lapa C. Volumetric and texture analysis of pretherapeutic 18F-FDG PET can predict overall survival in medullary thyroid cancer patients treated with Vandetanib. Endocrine. 2019;63:293–300.

    Article  CAS  PubMed  Google Scholar 

  62. Puhr-Westerheide D, Cyran CC, Sargsyan-Bergmann J, Todica A, Gildehaus FJ, Kunz WG, Stahl R, Spitzweg C, Ricke J, Kazmierczak PM. The added diagnostic value of complementary gadoxetic acid-enhanced MRI to 18F-DOPA-PET/CT for liver staging in medullary thyroid carcinoma. Cancer Imaging. 2019;14:19:73.

    Article  Google Scholar 

  63. Treglia G, Castaldi P, Villani MF, Perotti G, de Waure C, Filice A, Ambrosini V, Cremonini N, Santimaria M, Versari A, Fanti S, Giordano A, Rufini V. 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. 2012;39:569–80.

    Article  CAS  PubMed  Google Scholar 

  64. Yamaga LYI, Cunha ML, Campos Neto GC, Garcia MRT, Yang JH, Camacho CP, Wagner J, Funari MBG. (68)Ga-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. 2017;44:1695–701.

    Article  CAS  PubMed  Google Scholar 

  65. Lee SW, Shim SR, Jeong SY, Kim SJ. Comparison of 5 different PET radiopharmaceuticals for the detection of recurrent medullary thyroid carcinoma: a Network Meta-analysis. Clin Nucl Med. 2020;45:341–8.

    Article  PubMed  Google Scholar 

  66. Pajak C, Cadili L, Nabata K, Wiseman SM. 68Ga-DOTATATE-PET shows promise for diagnosis of recurrent or persistent medullary thyroid cancer: a systematic review. Am J Surg. 2022;224:670–5.

    Article  PubMed  Google Scholar 

  67. Treglia G, Tamburello A, Giovanella L. Detection rate of somatostatin receptor PET in patients with recurrent medullary thyroid carcinoma: a systematic review and a meta-analysis. Hormones (Athens Greece). 2017;16:262–72.

    Google Scholar 

  68. Reubi JC, Waser B, Maecke HR, Rivier JE. Highly increased 125i-Jr11 antagonist binding in vitro reveals novel indications for Sst2 targeting in human cancers. J Nucl Med. 2016;58:300–6.

    Article  PubMed  Google Scholar 

  69. Imperiale A, Jha A, Meuter L, Nicolas GP, Taïeb D, Pacak K. The emergence of somatostatin antagonist-based theranostics: paving the Road toward another success? J Nucl Med. 2023;64:682–4.

    Article  PubMed  PubMed Central  Google Scholar 

  70. Ueda CE, Duarte PS, de Castroneves LA, Coura-Filho GB, Sado HN, Sapienza MT, Hoff AO, Buchpiguel CA. Comparison of 18F-NaF PET/CT with other imaging methods in the detection of bone metastases in patients with medullary thyroid cancer: a report of a series of 31 cases. Nucl Med Mol Imaging. 2020;54:281–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Ueda CE, Duarte PS, de Castroneves LA, Flávio J, Marin G, Sado HN, Sapienza MT, Hoff AO, Buchpiguel CA. Burden of metastatic bone disease measured on 18F-NaF PET/computed tomography studies as a prognostic indicator in patients with medullary thyroid cancer. Nucl Med Commun. 2020;41:469–760.

    Article  CAS  PubMed  Google Scholar 

  72. Li C, Zhang P, Nie R, Gong X, Xie J, Yu Z, Wang C, Zhang H, Yan R, Lu Z. Targeting amyloids with [18F]AV-45 for medullary thyroid carcinoma positron emission tomography/computed tomography imaging: a pilot clinical study. Mol Pharm. 2022;19:584–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Jamsek J, Hocevar M, Bergant D, Zaletel K, Rep S, Lezaic L. Diagnostic value of [18F]Fluorocholine PET/CT in detection of primary medullary thyroid cancer. Ann Nucl Med. 2021;35:429–37.

    Article  CAS  PubMed  Google Scholar 

  74. Jang HW, Choi JY, Lee JI, Kim HK, Shin HW, Shin JH, Kim SW, Chung JH. Localization of medullary thyroid carcinoma after surgery using (11)C-methionine PET/CT: comparison with (18)F-FDG PET/CT. Endocr J. 2010;57:1045–54.

    Article  PubMed  Google Scholar 

  75. Uprimny C, von Guggenberg E, Svirydenka A, Mikołajczak R, Hubalewska-Dydejczyk A, Virgolini IJ. Comparison of PET/CT imaging with FDOPA and cholecystokinin-2 receptor targeting 68Ga-DOTA-MGS5 in a patient with advanced medullary thyroid carcinoma. Eur J Nucl Med Mol Imaging. 2021;48:935–6.

    Article  CAS  PubMed  Google Scholar 

  76. Sauter AW, Mansi R, Hassiepen U, Muller L, Panigada T, Wiehr S, Wild AM, Geistlich S, Béhé M, Rottenburger C, Wild D, Fani M. Targeting of the cholecystokinin-2 receptor with the minigastrin analog 177Lu-DOTA-PP-F11N:does the use of protease inhibitors further improve in vivo distribution? J Nucl Med. 2019;60:393–9.

    Article  CAS  PubMed  Google Scholar 

  77. von Guggenberg E, Uprimny C, Klingler M, Warwitz B, Sviridenko A, Bayerschmidt S, Di Santo G, Virgolini IJ. Preliminary clinical experience of cholecystokinin-2 receptor PET/CT imaging using the 68Ga-labeled minigastrin analog DOTA-MGS5 in patients with medullary thyroid cancer. J Nucl Med. 2023 (Ahead of print).

  78. Wong JYC, Yamauchi DM, Adhikarla V, Simpson J, Frankel PH, Fong Y, Melstrom KA, Chen YJ, Salehian BD, Woo Y, Dandapani SV, Colcher DM, Poku EK, Yazaki PJ, Wu AM, Shively JE. First-In-human pilot PET immunoimaging study of 64Cu-anti-carcinoembryonic antigen monoclonal antibody (hT84.66-M5A) in patients with carcinoembryonic antigen-producing cancers. Cancer Biother Radiopharm. 2023;38:26–37.

    CAS  PubMed  Google Scholar 

  79. Bodet-Milin C, Faivre-Chauvet A, Carlier T, Ansquer C, Rauscher A, Frampas E, Toulgoat F, Masson D, Bourgeois M, Cerato E, Rohmer V, Couturier O, Drui D, Goldenberg DM, Sharkey RM, Barbet J, Kraeber-Bodere F. Anti-CEA pretargeted immuno-PET shows higher sensitivity than DOPA PET/CT in detecting relapsing metastatic medullary thyroid carcinoma: Post hoc analysis of the iPET-MTC study. J Nucl Med. 2021;62:1221–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Bodet-Milin C, Bailly C, Touchefeu Y, Frampas E, Bourgeois M, Rauscher A, Lacoeuille F, Drui D, Arlicot N, Goldenberg DM, Faivre-Chauvet A, Barbet J, Rousseau C, Kraeber-Bodéré F. Clinical results in medullary thyroid carcinoma suggest high potential of pretargeted immuno-PET for tumor imaging and theranostic approaches. Front Med. 2019;6:124.

    Article  Google Scholar 

  81. Ballal S, Yadav MP, Moon ES, Rösch F, ArunRaj ST, Agarwal S, Tripathi M, Sahoo RK, Bal C. First-in-human experience with 177Lu-DOTAGA.(SA.FAPi)2 therapy in an uncommon case of aggressive medullary thyroid carcinoma clinically mimicking as anaplastic thyroid cancer. Clin Nucl Med. 2022;47:e444–5.

    Article  PubMed  Google Scholar 

  82. Kuyumcu S, Isık EG, Sanli Y. Liver metastases from medullary thyroid carcinoma detected on 68Ga-FAPI-04 PET/CT. Endocrine. 2021;74:727–8.

    Article  CAS  PubMed  Google Scholar 

  83. Ballal S, Yadav MP, Roesch F, Raju S, Satapathy S, Sheokand P, Moon ES, Martin M, Agarwal S, Tripathi M, Bal C. Head-to-head comparison of [68Ga]Ga-DOTA.SA.FAPi and [68Ga]Ga-DOTANOC PET/CT imaging for the follow-up surveillance of patients with medullary thyroid cancer. Thyroid. 2023;12 (Ahead of print).

  84. Arora S, Damle NA, Parida GK, Singhal A, Nalli H, Dattagupta S, Bal C. Recurrent medullary thyroid carcinoma on 68Ga-prostate-specific membrane antigen PET/CT: exploring new theranostic avenues. Clin Nucl Med. 2018;43:359–60.

    Article  PubMed  Google Scholar 

  85. Haddad RI, Bischoff L, Ball D, Bernet V, Blomain E, Busaidy NL, Campbell M, Dickson P, Duh QY, Ehya H, Goldner WS, Guo T, Haymart M, Holt S, Hunt JP, Iagaru A, Kandeel F, Lamonica DM, Mandel S, Markovina S, McIver B, Raeburn CD, Rezaee R, Ridge JA, Roth MY, Scheri RP, Shah JP, Sipos JA, Sippel R, Sturgeon C, Wang TN, Wirth LJ, Wong RJ, Yeh M, Cassara CJ, Darlow S. Thyroid carcinoma, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2022;20:925–51.

    Article  CAS  PubMed  Google Scholar 

  86. Hofland J, Brabander T, Verburg FA, Feelders RA, de Herder WW. Peptide receptor Radionuclide Therapy. J Clin Endocrinol Metab. 2022;107:3199–208.

    Article  PubMed  PubMed Central  Google Scholar 

  87. Czajkowski M, Kaemmerer D, Sänger J, Sauter G, Wirtz RM, Schulz S, Lupp A. Comparative evaluation of somatostatin and CXCR4 receptor expression in different types of thyroid carcinoma using well-characterised monoclonal antibodies. BMC Cancer. 2022;7:22:740.

    Article  Google Scholar 

  88. Hayes AR, Crawford A, Al Riyami K, Tang C, Bomanji J, Baldeweg SE, Wild D, Morganstein D, Harry A, Grozinsky-Glasberg S, Oleinikov K, Khoo B, Caplin ME, Nicolas GP, Grossman AB. Metastatic medullary thyroid Cancer: the role of 68Gallium-DOTA-Somatostatin Analogue PET/CT and peptide receptor Radionuclide Therapy. J Clin Endocrinol Metab. 2021;106:e4903–16.

    PubMed  Google Scholar 

  89. Maghsoomi Z, Emami Z, Malboosbaf R, Malek M, Khamseh ME. Efficacy and safety of peptide receptor radionuclide therapy in advanced radioiodine-refractory differentiated thyroid cancer and metastatic medullary thyroid cancer: a systematic review. BMC Cancer. 2021;20:21:579.

    Article  Google Scholar 

  90. Liu Q, Kulkarni HR, Zhao T, Schuchardt C, Chen X, Zhu Z, Zhang J, Baum RP. Peptide receptor Radionuclide Therapy in patients with Advanced Progressive Medullary thyroid Cancer: efficacy, Safety, and survival predictors. Clin Nucl Med. 2023;48:221–7.

    Article  PubMed  Google Scholar 

  91. von Guggenberg E, Kolenc P, Rottenburger C, Mikołajczak R, Hubalewska-Dydejczyk A. Update on Preclinical Development and clinical translation of Cholecystokinin-2 receptor targeting Radiopharmaceuticals. Cancers (Basel). 2021;18:13:5776.

    Article  Google Scholar 

  92. Hasenauer N, Higuchi T, Deschler-Baier B, Hartrampf PE, Pomper MG, Rowe SP, Fassnacht M, Buck AK, Werner RA. Visualization of Tumor Heterogeneity in Advanced Medullary thyroid carcinoma by Dual-Tracer Molecular Imaging: revealing the Theranostic potential of SSTR- and PSMA-Directed Endoradiotherapy. Clin Nucl Med. 2022;47:651–2.

    Article  PubMed  Google Scholar 

  93. Martin M, Ballal S, Yadav MP, Bal C, Van Rymenant Y, De Loose J, Verhulst E, De Meester I, Van Der Veken P, Roesch F. Novel generation of FAP inhibitor-based homodimers for Improved Application in Radiotheranostics. Cancers (Basel). 2023;21;15:1889.

  94. Kim M, Kim BH. Current guidelines for management of medullary thyroid carcinoma. Endocrinol Metab (Seoul). 2021;36:514–24.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Nuclear Medicine and Molecular Imaging, Institut de Cancérologie de Strasbourg Europe (ICANS), Strasbourg University Hospitals, Strasbourg, France

    Alessio Imperiale

  2. Molecular Imaging, DRHIM, Institut Pluridisciplinaire Hubert Curien (IPHC), UMR7178, CNRS, University of Strasbourg, Strasbourg, France

    Alessio Imperiale

  3. Nuclear Medicine, Department of Experimental and Clinical Biomedical Sciences ’Mario Serio’, University of Florence, Florence, Italy

    Valentina Berti

  4. Medical Oncology, Institut de Cancérologie de Strasbourg Europe (ICANS), Strasbourg, France

    Mickaël Burgy

  5. Laboratory of Bioimaging and Pathology, University of Strasbourg, UMR7021 CNRS, Illkirch, 67401, France

    Mickaël Burgy

  6. Interventional Radiology, Strasbourg University Hospitals, Strasbourg University, Strasbourg, France

    Roberto Luigi Cazzato

  7. Nuclear Medicine, Ente Ospedaliero Ospedali Galliera, Genoa, Italy

    Arnoldo Piccardo

  8. Clinic for Nuclear Medicine, Imaging Institute of Southern Switzerland, Ente Ospedaliero Cantonale, Bellinzona, Switzerland

    Giorgio Treglia

  9. Nuclear Medicine and Molecular Imaging, Lausanne University Hospital, Lausanne, Switzerland

    Giorgio Treglia

  10. Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland

    Giorgio Treglia

  11. Faculty of Biomedical Sciences, Università della Svizzera Italiana, Lugano, Switzerland

    Giorgio Treglia

Authors
  1. Alessio Imperiale
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Valentina Berti
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mickaël Burgy
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Roberto Luigi Cazzato
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Arnoldo Piccardo
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Giorgio Treglia
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Alessio Imperiale.

Ethics declarations

Competing interests

The authors declare that they have no conflict of interest.

Additional information

Publisher’s Note

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

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Imperiale, A., Berti, V., Burgy, M. et al. Molecular imaging and related therapeutic options for medullary thyroid carcinoma: state of the art and future opportunities. Rev Endocr Metab Disord 25, 187–202 (2024). https://doi.org/10.1007/s11154-023-09836-y

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11154-023-09836-y

Keywords

Search

Navigation