Advertisement

Additional value of integrated 18F-choline PET/4D contrast-enhanced CT in the localization of hyperfunctioning parathyroid glands and correlation with molecular profile

  • Arnoldo Piccardo
  • P. Trimboli
  • M. Rutigliani
  • M. Puntoni
  • L. Foppiani
  • L. Bacigalupo
  • Anna Crescenzi
  • G. Bottoni
  • G. Treglia
  • F. Paparo
  • P. Del Monte
  • M. Lanata
  • G. Paone
  • G. Ferrarazzo
  • U. Catrambone
  • A. Arlandini
  • L. Ceriani
  • M. Cabria
  • L. Giovanella
Original Article
  • 97 Downloads

Abstract

Purpose

The localization of hyperfunctioning parathyroid gland(s) (HPTG) in patients with primary hyperparathyroidism (PHPT) with negative or inconclusive first-line imaging is a significant challenge. This study aimed to evaluate the role of integrated 18F-choline PET/4D contrast-enhanced computed tomography (4DCeCT) in these patients, compare its detection rate and sensitivity with those of 18F-choline PET/CT and (4DCeCT), and analyse the association between choline metabolism and morphological, biochemical and molecular parameters of HPTG.

Methods

We prospectively enrolled 44 PHPT patients with negative or inconclusive first-line imaging. 18F-Choline PET/CT and 4DCeCT were performed at the same time, and integrated 18F-choline PET/4DCeCT images were obtained after coregistration. Experienced physicians examined the images. The SUVratio and degree of contrast enhancement were recorded for each positive finding. Histopathology, laboratory and multidisciplinary follow-up were used as the standard of reference. Both the detection rates and sensitivities of the three imaging modalities were calculated retrospectively. Immunohistochemistry was performed to evaluate the molecular profile of HPTGs.

Results

18F-Choline PET/4DCeCT was positive in 32 of 44 patients with PHPT (detection rate 72.7%), and 31 of 31 surgically treated patients (sensitivity 100%). These results were significantly (p < 0.05) better than those of 18F-choline PET/CT (56.8% and 80%, respectively) and those of 4DCeCT (54.5 and 74%, respectively). A significant correlation between SUV and calcium level was found. In a multivariate analysis, only calcium level was significantly associated with 18F-choline PET/4DCeCT findings. SUVratio and Ki67 expression were significantly correlated.

Conclusion

Integrated 18F-choline PET/4DCeCT should be considered as an effective tool to detect PHPT in patients with negative or inconclusive first-line imaging. Choline metabolism is correlated with both calcium level and Ki67 expression in HPTG.

Keywords

Hyperparathyroidism 18F-Choline Elderly 4DCeCT Molecular profile 

Notes

Funding

This research did not receive any specific grant from any funding agency in the public, commercial or nonprofit sector.

Compliance with ethical standards

Conflicts of interest

None.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the principles of the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

Informed consent

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

References

  1. 1.
    Silverberg SJ. Natural history of primary hyperparathyroidism. Endocrinol Metab Clin N Am. 2000;29(3):451–64.CrossRefGoogle Scholar
  2. 2.
    Singh Ospina NM, Rodriguez-Gutierrez R, Maraka S, Espinosa de Ycaza AE, Jasim S, Castaneda-Guarderas A, et al. Outcomes of parathyroidectomy in patients with primary hyperparathyroidism: a systematic review and meta-analysis. World J Surg. 2016;40(10):2359–77.  https://doi.org/10.1007/s00268-016-3514-1.CrossRefPubMedGoogle Scholar
  3. 3.
    Bilezikian JP, Brandi ML, Eastell R, Silverberg SJ, Udelsman R, Marcocci C, et al. Guidelines for the management of asymptomatic primary hyperparathyroidism: summary statement from the Fourth International Workshop. J Clin Endocrinol Metab. 2014;99(10):3561–9.CrossRefGoogle Scholar
  4. 4.
    Noussios G, Anagnostis P, Natsis K. Ectopic parathyroid glands and their anatomical, clinical and surgical implications. Exp Clin Endocrinol Diabetes. 2012;120(10):604–10.CrossRefGoogle Scholar
  5. 5.
    Treglia G, Sadeghi R, Schalin-Jäntti C, Caldarella C, Ceriani L, Giovanella L, et al. Detection rate of (99m) Tc-MIBI single photon emission computed tomography (SPECT)/CT in preoperative planning for patients with primary hyperparathyroidism: a meta-analysis. Head Neck. 2016;381:E2159–72.CrossRefGoogle Scholar
  6. 6.
    Lo CY, Lang BH, Chan WF, Kung AW, Lam KSA. Prospective evaluation of preoperative localization by technetium-99m sestamibi scintigraphy and ultrasonography in primary hyperparathyroidism. Am J Surg. 2007;193:155–9.CrossRefGoogle Scholar
  7. 7.
    Harari A, Mitmaker E, Grogan RH, Lee J, Shen W, Gosnell J, et al. Primary hyperparathyroidism patients with positive preoperative sestamibi scan and negative ultrasound are more likely to have posteriorly located upper gland adenomas (PLUGs). Ann Surg Oncol. 2011;18:1717–22.CrossRefGoogle Scholar
  8. 8.
    Treglia G, Trimboli P, Huellner M, Giovanella L. Imaging in primary hyperparathyroidism: focus on the evidence-based diagnostic performance of different methods. Minerva Endocrinol. 2018;43(2):133–43.PubMedGoogle Scholar
  9. 9.
    Minisola S, Cipriani C, Diacinti D, Tartaglia F, Scillitani A, Pepe J, et al. Imaging of the parathyroid glands in primary hyperparathyroidism. Eur J Endocrinol. 2016;174(1):D1–8.CrossRefGoogle Scholar
  10. 10.
    Starker LF, Mahajan A, Bjorklund P, Sze G, Udelsman R, Carling T. 4D parathyroid CT as the initial localization study for patients with de novo primary hyperparathyroidism. Ann Surg Oncol. 2011;18:1723–8.CrossRefGoogle Scholar
  11. 11.
    Mekel M, Linder R, Bishara B, Kluger Y, Bar-On O, Fischer D. 4-dimensional computed tomography for localization of parathyroid adenoma. Harefuah. 2013;152:710–2.PubMedGoogle Scholar
  12. 12.
    Hamidi M, Sullivan M, Hunter G, Hamberg L, Cho NL, Gawande AA, et al. 4D-CT is superior to ultrasound and sestamibi for localizing recurrent parathyroid disease. Ann Surg Oncol. 2018;25(5):1403–9.CrossRefGoogle Scholar
  13. 13.
    Tian Y, Tanny ST, Einsiedel P, Lichtenstein M, Stella DL, Phal PM, et al. Four-dimensional computed tomography: clinical impact for patients with primary hyperparathyroidism. Ann Surg Oncol. 2018;25:117–21.  https://doi.org/10.1245/s10434-017-6115-9.CrossRefPubMedGoogle Scholar
  14. 14.
    Quak E, Lheureux S, Reznik Y, Bardet S, Aide N. F18-choline, a novel PET tracer for parathyroid adenoma? J Clin Endocrinol Metab. 2013;98:3111–2.CrossRefGoogle Scholar
  15. 15.
    Hodolic M, Huchet V, Balogova S, Michaud L, Kerrou K, Nataf V, et al. Incidental uptake of (18)F-fluorocholine (FCH) in the head or in the neck of patients with prostate cancer. Radiol Oncol. 2014;48:228–34.CrossRefGoogle Scholar
  16. 16.
    Cazaentre T, Clivaz F, Triponez F. False-positive result in 18F-fluorocholine PET/CT due to incidental and ectopic parathyroid hyperplasia. Clin Nucl Med. 2014;39:e328–30.CrossRefGoogle Scholar
  17. 17.
    Michaud L, Burgess A, Huchet V, Lefèvre M, Tassart M, Ohnona J, et al. Is 18F-fluorocholine-positron emission tomography/computerized tomography a new imaging tool for detecting hyperfunctioning parathyroid glands in primary or secondary hyperparathyroidism? J Clin Endocrinol Metab. 2014;99:4531–6.CrossRefGoogle Scholar
  18. 18.
    Orevi M, Freedman N, Mishani E, Bocher M, Jacobson O, Krausz Y. Localization of parathyroid adenoma by 11C-choline PET/CT: preliminary results. Clin Nucl Med. 2014;39:1033–8.CrossRefGoogle Scholar
  19. 19.
    Lezaic L, Rep S, Sever MJ, Kocjan T, Hocevar M, Fettich J. 18F-Fluorocholine PET/CT for localization of hyperfunctioning parathyroid tissue in primary hyperparathyroidism: a pilot study. Eur J Nucl Med Mol Imaging. 2014;41:2083–9.CrossRefGoogle Scholar
  20. 20.
    Michaud L, Balogova S, Burgess A, Ohnona J, Huchet V, Kerrou K, et al. A pilot comparison of 18f-fluorocholine PET/CT, ultrasonography and 123i/99mtc-sestamibi dual-phase dual-isotope scintigraphy in the preoperative localization of hyperfunctioning parathyroid glands in primary or secondary hyperparathyroidism: influence of thyroid anomalies. Medicine (Baltimore). 2015;94:e1701.CrossRefGoogle Scholar
  21. 21.
    Quak E, Blanchard D, Houdu B, Le Roux Y, Ciappuccini R, Lireux B, et al. F18-choline PET/CT guided surgery in primary hyperparathyroidism when ultrasound and MIBI SPECT/CT are negative or inconclusive: the APACH1 study. Eur J Nucl Med Mol Imaging. 2018;45(4):658–66.CrossRefGoogle Scholar
  22. 22.
    Grimaldi S, Young J, Kamenicky P, Hartl D, Terroir M, Leboulleux S, et al. Challenging pre-surgical localization of hyperfunctioning parathyroid glands in primary hyperparathyroidism: the added value of (18)F-fluorocholine PET/CT. Eur J Nucl Med Mol Imaging. 2018;45(10):1772–80.  https://doi.org/10.1007/s00259-018-4018-z.CrossRefPubMedGoogle Scholar
  23. 23.
    Taywade SK, Damle NA, Behera A, Devasenathipathy K, Bal C, Tripathi M, et al. Comparison of 18F-fluorocholine positron emission tomography/computed tomography and four-dimensional computed tomography in the preoperative localization of parathyroid adenomas – initial results. Indian J Endocrinol Metab. 2017;21(3):399–403.CrossRefGoogle Scholar
  24. 24.
    Kluijfhout WP, Pasternak JD, Gosnell JE, Shen WT, Duh QY, Vriens MR, et al. (18)F fluorocholine PET/MR imaging in patients with primary hyperparathyroidism and inconclusive conventional imaging: a prospective pilot study. Radiology. 2017;284(2):460–7.CrossRefGoogle Scholar
  25. 25.
    Beheshti M, Hehenwarter L, Paymani Z, Rendl G, Imamovic L, Rettenbacher R, et al. (18)F-Fluorocholine PET/CT in the assessment of primary hyperparathyroidism compared with (99m)Tc-MIBI or (99m)Tc-tetrofosmin SPECT/CT: a prospective dual-centre study in 100 patients. Eur J Nucl Med Mol Imaging. 2018;45(10):1762–71.  https://doi.org/10.1007/s00259-018-3980-9.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Lloyd RV, Osamura RY, Kloppel G, Rosai J. WHO Classification of Tumours of Endocrine Organs: WHO Classification of Tumours, 4th Edition, Volume 10. Lyon: International Agency for Research on Cancer, 2017.Google Scholar
  27. 27.
    Krakauer M, Wieslander B, Myschetzky PS, Lundstrøm A, Bacher T, Sørensen CH, et al. A prospective comparative study of parathyroid dual-phase scintigraphy, dual-isotope subtraction scintigraphy, D-CT, and ultrasonography in primary hyperparathyroidism. Clin Nucl Med. 2016;41:93–100.CrossRefGoogle Scholar
  28. 28.
    Lumachi F, Zucchetta P, Marzola MC, Boccagni P, Angelini F, Bui F, et al. Advantages of combined technetium-99m-sestamibi scintigraphy and high-resolution ultrasonography in parathyroid localization: comparative study in 91 patients with primary hyperparathyroidism. Eur J Endocrinol. 2000;143:755–60.CrossRefGoogle Scholar
  29. 29.
    Alharbi AA, Alshehri FM, Albatly AA, Sah BR, Schmid C, Huber GF, et al. [(18)F]Fluorocholine uptake of parathyroid adenoma is correlated with parathyroid hormone level. Mol Imaging Biol. 2018.  https://doi.org/10.1007/s11307-018-1179-x.CrossRefPubMedGoogle Scholar
  30. 30.
    Melloul M, Paz A, Koren R, Cytron S, Feinmesser R, Gal R. 99mTc-MIBI scintigraphy of parathyroid adenomas and its relation to tumour size and oxyphil cell abundance. Eur J Nucl Med. 2001;28:209–13.CrossRefGoogle Scholar
  31. 31.
    Chen CC, Skarulis MC, Fraker DL, Alexander R, Marx SJ, Spiegel AM. Technetium-99m-sestamibi imaging before reoperation for primary hyperparathyroidism. J Nucl Med. 1995;36:2186–91.PubMedGoogle Scholar
  32. 32.
    Kluijfhout WP, Vorselaars WM, van den Berk SA, Vriens MR, Borel Rinkes IH, Valk GD, et al. Fluorine-18 fluorocholine PET-CT localizes hyperparathyroidism in patients with inconclusive conventional imaging: a multicenter study from the Netherlands. Nucl Med Commun. 2016;37:1246–52.CrossRefGoogle Scholar
  33. 33.
    Treglia G, Piccardo A, Imperiale A, Strobel K, Kaufmann PA, Prior JO, et al. Diagnostic performance of choline PET for detection of hyperfunctioning parathyroid glands in hyperparathyroidism: a systematic review and meta-analysis. Eur J Nucl Med Mol Imaging. 2018.  https://doi.org/10.1007/s00259-018-4123-z.CrossRefPubMedGoogle Scholar
  34. 34.
    Piñero A, Rodríguez JM, Martínez-Barba E, Canteras M, Stiges-Serra A, Parrilla P. Tc99m-sestamibi scintigraphy and cell proliferation in primary hyperparathyroidism: a causal or casual relationship? Surgery. 2003;134(1):41–4.CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Arnoldo Piccardo
    • 1
    • 2
  • P. Trimboli
    • 2
  • M. Rutigliani
    • 3
  • M. Puntoni
    • 4
  • L. Foppiani
    • 5
  • L. Bacigalupo
    • 6
  • Anna Crescenzi
    • 7
  • G. Bottoni
    • 1
  • G. Treglia
    • 2
    • 8
  • F. Paparo
    • 6
  • P. Del Monte
    • 9
  • M. Lanata
    • 3
  • G. Paone
    • 2
  • G. Ferrarazzo
    • 1
  • U. Catrambone
    • 10
  • A. Arlandini
    • 10
  • L. Ceriani
    • 2
  • M. Cabria
    • 1
  • L. Giovanella
    • 2
  1. 1.Department of Nuclear MedicineGalliera HospitalGenoaItaly
  2. 2.Department of Nuclear Medicine and PET/CT CentreOncology Institute of Southern SwitzerlandBellinzonaSwitzerland
  3. 3.Department of HistopathologyGalliera HospitalGenoaItaly
  4. 4.Clinical Trial Unit, Office of the Scientific DirectorGalliera HospitalGenoaItaly
  5. 5.Department of Internal MedicineGalliera HospitalGenoaItaly
  6. 6.Department of RadiologyGalliera HospitalGenoaItaly
  7. 7.Pathology UnitUniversity Hospital Campus Bio MedicoRomeItaly
  8. 8.Department of Nuclear Medicine and Molecular ImagingLausanne University HospitalLausanneSwitzerland
  9. 9.Department of EndocrinologyGalliera HospitalGenoaItaly
  10. 10.Department of SurgeryGalliera HospitalGenoaItaly

Personalised recommendations