Skip to main content
Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging 3/2019

15.09.2018 | Original Article

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

verfasst von: 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

Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging | Ausgabe 3/2019

Einloggen, um Zugang zu erhalten

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.
Literatur
1.
Zurück zum Zitat Silverberg SJ. Natural history of primary hyperparathyroidism. Endocrinol Metab Clin N Am. 2000;29(3):451–64.CrossRef Silverberg SJ. Natural history of primary hyperparathyroidism. Endocrinol Metab Clin N Am. 2000;29(3):451–64.CrossRef
3.
Zurück zum Zitat 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
4.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
5.
Zurück zum Zitat 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.CrossRef 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.CrossRef
6.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
7.
Zurück zum Zitat 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
8.
Zurück zum Zitat 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.PubMed 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.PubMed
9.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
10.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
11.
Zurück zum Zitat 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.PubMed 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.PubMed
12.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
14.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
15.
Zurück zum Zitat 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
16.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
17.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
18.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
19.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
20.
Zurück zum Zitat 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.CrossRef 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.CrossRef
21.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
22.
23.
Zurück zum Zitat 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
24.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
26.
Zurück zum Zitat 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. 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.
27.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
28.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
30.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
31.
Zurück zum Zitat 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.PubMed 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.PubMed
32.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
34.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
Metadaten
Titel
Additional value of integrated 18F-choline PET/4D contrast-enhanced CT in the localization of hyperfunctioning parathyroid glands and correlation with molecular profile
verfasst von
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
Publikationsdatum
15.09.2018
Verlag
Springer Berlin Heidelberg
Erschienen in
European Journal of Nuclear Medicine and Molecular Imaging / Ausgabe 3/2019
Print ISSN: 1619-7070
Elektronische ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-018-4147-4

Weitere Artikel der Ausgabe 3/2019

European Journal of Nuclear Medicine and Molecular Imaging 3/2019 Zur Ausgabe