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Hepatology International

, Volume 8, Issue 4, pp 493–500 | Cite as

Diagnostic role of radiolabelled choline PET or PET/CT in hepatocellular carcinoma: a systematic review and meta-analysis

  • Francesco BertagnaEmail author
  • Mattia Bertoli
  • Giovanni Bosio
  • Giorgio Biasiotto
  • Ramin Sadeghi
  • Raffaele Giubbini
  • Giorgio Treglia
Review Article

Abstract

The role of fluorine-18-fluorodeoxygluose positron emission tomography/computed tomography (18F-FDG PET/CT) in hepatocellular carcinoma (HCC) has not been firmly established yet and its sensitivity has been reported to be in the range of 40–60 %. Because of this relatively low sensitivity alternative tracers have been proposed. The aim of our review is to analyse the literature data on the diagnostic role of 18F/11C-choline PET/CT in the evaluation of HCC. A comprehensive computer literature search of PubMed/MEDLINE, Embase and Scopus databases was conducted to find relevant published articles about the role of whole-body 18F-choline or 11C-choline PET or PET/CT in patients with HCC. Furthermore, a meta-analysis about the detection rate of this method in HCC was performed. Six articles were included in this systematic review and discussed. The meta-analysis of five out of six articles showed a DR of 84 % (95 % CI 79–89 %). The DR increased when poorly differentiated HCC was excluded from the analysis. Radiolabelled choline PET or PET/CT could be a valuable tool in detecting HCC and it is better than 18F-FDG PET/CT, especially in well to moderately differentiated lesions; on the other hand, poorly differentiated and higher-stage HCC could be better evaluated with 18F-FDG and dual tracer imaging should be considered and could be potentially useful to increase accuracy.

Keywords

18F-choline 11C-choline HCC Hepatocellular carcinoma PET/CT 

Notes

Compliance with ethical requirements and Conflict of interest

All procedures were in accordance with the ethical standards of the responsible committee on human experimentation and with the Helsinki Declaration. Francesco Bertagna, Mattia Bertoli, Giovanni Bosio, Giorgio Biasiotto, Ramin Sadeghi, Raffaele Giubbini and Giorgio Treglia declare that they have no conflict of interest.

References

  1. 1.
    Okuda K. Hepatocellular carcinoma. J Hepatol. 2000;32:225–237PubMedCrossRefGoogle Scholar
  2. 2.
    Parkin DM, Bray F, Ferlay J, Pisani P. Global Cancer Statistics, 2002. CA Cancer J Clin. 2005;55:74–108PubMedCrossRefGoogle Scholar
  3. 3.
    Parkin DM, Bray F, Ferlay J, Pisani P. Estimating the world cancer burden: Globocan 2000. Int J Cancer. 2001;94:153–156PubMedCrossRefGoogle Scholar
  4. 4.
    Hussain SM, Semelka RC, Mitchell DG. MR imaging of hepatocellular carcinoma. Magn Reson Imaging Clin N Am. 2002;10:31–52PubMedCrossRefGoogle Scholar
  5. 5.
    Lee KHY, O’Malley ME, Kachura JR, Haider M, Hanbidge A. Hepatocellular carcinoma: imaging and imaging guided intervention. Am J Roentgenol. 2003;180:1015–1022CrossRefGoogle Scholar
  6. 6.
    Wudel LJ Jr, Delbeke D, Morris D, Rice M, Washington MK, Shyr Y, et al. The role of [18F]fluorodeoxyglucose positron emission tomography imaging in the evaluation of hepatocellular carcinoma. Am Surg. 2003;69:117–124PubMedGoogle Scholar
  7. 7.
    Paudyal B, Paudyal P, Oriuchi N, Tsushima Y, Nakajima T, Endo K. Clinical implication of glucose transport and metabolism evaluated by 18F-FDG PET in hepatocellular carcinoma. Int J Oncol. 2008;33:1047–1054PubMedGoogle Scholar
  8. 8.
    Okazumi S, Isono K, Enomoto K, Kikuchi T, Ozaki M, Yamamoto H, et al. Evaluation of liver tumors using fluorine-18-fluorodexyglucose PET: characterization of tumor and assessment of effect of treatment. J Nucl Med. 1992;33:333–339PubMedGoogle Scholar
  9. 9.
    Delbeke D, Martin WH, Sandler MP, Chapman WC, Wright JK Jr, Pinson CW. Evaluation of benign vs malignant hepatic lesions with positron emission tomography. Arch Surg. 1998;133:510–515PubMedCrossRefGoogle Scholar
  10. 10.
    Trojan J, Schroeder O, Raedle J, Baum RP, Herrmann G, Jacobi V, et al. Fluorine-18 FDG positron emission tomography for imaging of hepatocellular carcinoma. Am J Gastroenterol. 1999;94:3314–3319PubMedCrossRefGoogle Scholar
  11. 11.
    Ho CL, Chen S, Yeung DW, Cheng TK. Dual-tracer PET/CT imaging in evaluation of metastatic hepatocellular carcinoma. J Nucl Med. 2007;48:902–909PubMedCrossRefGoogle Scholar
  12. 12.
    Ho CL, Yu SC, Yeung DW. 11C-acetate PET imaging in hepatocellular carcinoma and other liver masses. J Nucl Med. 2003;44:213–221PubMedGoogle Scholar
  13. 13.
    Hwang KH, Choi DJ, Lee SY, Lee MK, Choe W. Evaluation of patients with hepatocellular carcinomas using [11C]acetate and [18F]FDG PET/CT: a preliminary study. Appl Radiat Isot. 2009;67:1195–1198PubMedCrossRefGoogle Scholar
  14. 14.
    Cheung TT, Ho CL, Lo CM, Chen S, Chan SC, Chok KS, et al. 11C-acetate and 18F-FDG PET/CT for clinical staging and selection of patients with hepatocellular carcinoma for liver transplantation on the basis of Milan criteria: surgeon’s perspective. J Nucl Med. 2013;54:192–200PubMedCrossRefGoogle Scholar
  15. 15.
    Barwick T, Zerizer I, Al-Nahhas A. Clinical dilemmas in primary liver cancer. Value of PET scanning. 2011. doi: 10.1002/9781119962205.ch17. Print ISBN: 9780470657973. Online ISBN: 9781119962205
  16. 16.
    Corn D, Jesberger J, Kolthammer J, Flask C, Lee Z. Dual-modality imaging of hepatocellular carcinoma. Cancer Res. 2011;71(Suppl 1). doi: 10.1158/1538-7445.AM2011-5297.
  17. 17.
    Goh V, Sarker D, Osmany S, Cook GJ. Functional imaging techniques in hepatocellular carcinoma. Eur J Nucl Med Mol Imaging. 2012;39:1070–1079PubMedCrossRefGoogle Scholar
  18. 18.
    He TT, Tian JH. Application of positron emission tomography molecular probes in hepatocellular carcinoma biological imaging. Chin Med Sci J. 2011;26(2):113–118PubMedCrossRefGoogle Scholar
  19. 19.
    Jadvar H. Hepatocellular carcinoma and gastroenteropancreatic neuroendocrine tumors: potential role of other positron emission tomography radiotracers. Semin Nucl Med. 2012;42:247–254PubMedGoogle Scholar
  20. 20.
    Kolthammer JA, Corn DJ, Wu C, Tenley NP, Wang Y, Lee Z. Same-session comparison of fluorocholine and choline for PET imaging of hepatocellular carcinoma. Mol Imaging Biol. 2010;12(Suppl 2):S1200Google Scholar
  21. 21.
    Kumar R, Chauhan A. Positron emission tomography: clinical applications in oncology. Part 2. Expert Rev Anticancer Ther. 2006;6(4):625–640PubMedCrossRefGoogle Scholar
  22. 22.
    Kwee SA, DeGrado TR, Talbot JN, Gutman F, Coel MN. Cancer imaging with fluorine-18-labeled choline derivatives. Semin Nucl Med. 2007;37:420–428PubMedCrossRefGoogle Scholar
  23. 23.
    Mertens K, Slaets D, Lambert B, Acou M, De Vos F, Goethals I. PET with (18)F-labelled choline-based tracers for tumour imaging: a review of the literature. Eur J Nucl Med Mol Imaging. 2010;37:2188–2193PubMedCrossRefGoogle Scholar
  24. 24.
    Skoura E, Datseris IE. The use of 18F-fluorothymidine and 18F-fluorocholine in imaging with positron emission tomography. Hell J Nucl Med. 2010;13:88–90PubMedGoogle Scholar
  25. 25.
    Treglia G, Giovannini E, Di Franco D, Calcagni ML, Rufini V, Picchio M, et al. The role of positron emission tomography using carbon-11 and fluorine-18 choline in tumors other than prostate cancer: a systematic review. Ann Nucl Med. 2012;26:451–461PubMedCrossRefGoogle Scholar
  26. 26.
    Vutrapongwatana U, Juiklom W, Wilaipraphakorn N, Suratako S, Sarasamkan J, Wongsa P, et al. Diagnosis in hepatocellular carcinoma using 11C-Choline PET/CT by comparison with 18F-FDG: Pilot study. Eur J Nucl Med Mol Imaging. 2011;38(Suppl 2):S373Google Scholar
  27. 27.
    Wong LL, Okimoto G, Kwee S. Pilot study of 18F-fluorocholine PET/CT of the liver in patients with hepatocellular cancer. HPB. 2011;13(Suppl 1):75Google Scholar
  28. 28.
    Lenzo NP, Anderson J, Campbell A, Morandeau L, De Grado TR. Fluoromethylcholine PET in recurrent multifocal hepatoma. Australas Radiol. 2007;51(Suppl 4):B299–B302PubMedCrossRefGoogle Scholar
  29. 29.
    Balogova S, Bumsel F, Kerrou K, Huchet V, Nataf V, Mal F, et al. Fluorocholine(18F) has a clinical usefulness in prostate cancer and in hepatocellular carcinoma sometimes in the same patient. Méd Nucl. 2010;34:378–382CrossRefGoogle Scholar
  30. 30.
    Bieze M, van Gulik TM, Bennink RJ. Hepatoblastoma evaluated by 18F-Fluoromethyl choline PET/CT. Clin Nucl Med. 2013;38:e80–e82PubMedCrossRefGoogle Scholar
  31. 31.
    Kolthammer JA, Corn DJ, Tenley N, Wu C, Tian H, Wang Y, et al. PET imaging of hepatocellular carcinoma with 18F-fluoroethylcholine and 11C-choline. Eur J Nucl Med Mol Imaging. 2011;38:1248–1256PubMedCrossRefGoogle Scholar
  32. 32.
    Kuang Y, Salem N, Corn DJ, Erokwu B, Tian H, Wang F, et al. Transport and metabolism of radiolabeled choline in hepatocellular carcinoma. Mol Pharm. 2010;7(6):2077–2092PubMedCrossRefPubMedCentralGoogle Scholar
  33. 33.
    Kuang Y, Salem N, Tian H, Kolthammer JA, Corn DJ, Wu C, et al. Imaging lipid synthesis in hepatocellular carcinoma with [methyl-11C]choline: correlation with in vivo metabolic studies. J Nucl Med. 2011;52:98–106PubMedCrossRefGoogle Scholar
  34. 34.
    Salem N, Kuang Y, Wang F, Maclennan GT, Lee Z. PET imaging of hepatocellular carcinoma with 2-deoxy-2[18F]fluoro-D-glucose, 6-deoxy-6[18F] fluoro-D-glucose, [1-11C]-acetate and [N-methyl-11C]-choline. Q J Nucl Med Mol Imaging. 2009;53:144–156PubMedGoogle Scholar
  35. 35.
    van den Esschert JW, Bieze M, Beuers UH, van Gulik TM, Bennink RJ. Differentiation of hepatocellular adenoma and focal nodular hyperplasia using 18F-fluorocholine PET/CT. Eur J Nucl Med Mol Imaging. 2011;38:436–440PubMedCrossRefPubMedCentralGoogle Scholar
  36. 36.
    Talbot JN, Gutman F, Fartoux L, Grange JD, Ganne N, Kerrou K, et al. PET/CT in patients with hepatocellular carcinoma using [(18)F]fluorocholine: preliminary comparison with [(18)F]FDG PET/CT. Eur J Nucl Med Mol Imaging. 2006;33:1285–1289PubMedCrossRefGoogle Scholar
  37. 37.
    Yamamoto Y, Nishiyama Y, Kameyama R, Okano K, Kashiwagi H, Deguchi A, et al. Detection of hepatocellular carcinoma using 11C-choline PET: comparison with 18F-FDG PET. J Nucl Med. 2008;49:1245–1248PubMedCrossRefGoogle Scholar
  38. 38.
    Talbot JN, Fartoux L, Balogova S, Nataf V, Kerrou K, Gutman F, et al. Detection of hepatocellular carcinoma with PET/CT: a prospective comparison of 18F-fluorocholine and 18F-FDG in patients with cirrhosis or chronic liver disease. J Nucl Med. 2010;51:1699–1706PubMedCrossRefGoogle Scholar
  39. 39.
    Wu HB, Wang QS, Li BY, Li HS, Zhou WL, Wang QY. F-18 FDG in conjunction with 11C-choline PET/CT in the diagnosis of hepatocellular carcinoma. Clin Nucl Med. 2011;36:1092–1097.PubMedCrossRefGoogle Scholar
  40. 40.
    Fartoux L, Balogova S, Nataf V, Kerrou K, Huchet V, Rosmorduc O, et al. A pilot comparison of 18F-fluorodeoxyglucose and 18F-fluorocholine PET/CT to predict early recurrence of unifocal hepatocellular carcinoma after surgical resection. Nucl Med Commun. 2012;33:757–765PubMedCrossRefGoogle Scholar
  41. 41.
    Bieze M, Klumpen HJ, Verheij J, Beuers U, Phoa SS, van Gulik TM, et al. Diagnostic accuracy of 18F-methyl-choline PET/CT for intra- and extrahepatic hepatocellular carcinoma. Hepatology. 2014;59:996–1006PubMedCrossRefGoogle Scholar
  42. 42.
    Tsurusaki M, Okada M, Kuroda H, Matsuki M, Ishii K, Murakami T. Clinical application of 18F-fluorodeoxyglucose positron emission tomography for assessment and evaluation after therapy for malignant hepatic tumor. J Gastroenterol. 2014;49:46–56PubMedCrossRefPubMedCentralGoogle Scholar
  43. 43.
    Bohm B, Voth M, Geoghegan J, Hellfritzsch H, Petrovich A, Scheele J, et al. Impact of positron emission tomography on strategy in liver resection for primary and secondary liver tumors. J Cancer Res Clin Oncol. 2004;130:266–272PubMedCrossRefGoogle Scholar
  44. 44.
    Vitola JV, Delbeke D, Sandler MP, Campbell MG, Powers TA, Wright JK, et al. Positron emission tomography to stage suspected metastatic colorectal carcinoma to the liver. Am J Surg. 1996;171:21–26PubMedCrossRefGoogle Scholar
  45. 45.
    Pant V, Sen IB, Soin AS. Role of 18F-FDG PET CT as an independent prognostic indicator in patients with hepatocellular carcinoma. Nucl Med Commun. 2013;34:749–757PubMedCrossRefGoogle Scholar
  46. 46.
    Shiomi S, Nishiguchi S, Ishizu H, Iwata Y, Sasaki N, Tamori A, et al. Usefulness of positron emission tomography with fluorine-18-fluorodeoxyglucose for predicting outcome in patients with hepatocellular carcinoma. Am J Gastroenterol. 2001;96:1877–1880PubMedCrossRefGoogle Scholar
  47. 47.
    Kong YH, Han CJ, Lee SD, Sohn WS, Kim MJ, Ki SS, et al. Positron emission tomography with fluorine-18-fluorodeoxyglucose is useful for predicting the prognosis of patients with hepatocellular carcinoma. Korean J Hepatol. 2004;10:279–287PubMedGoogle Scholar
  48. 48.
    Li CW, Kuo YC, Chen CY, Kuo YT, Chiu YY, She FO, et al. Quantification of choline compounds in human hepatic tumors by proton MR spectroscopy at 3 T. Magn Reson Med. 2005;53:770–776PubMedCrossRefGoogle Scholar
  49. 49.
    Roivainen A, Forsback S, Gronroos T, Lehikoinen P, Kähkönen M, Sutinen E, et al. Blood metabolism of [methyl-11C]choline, implications for in vivo imaging with positron emission tomography. Eur J Nucl Med. 2000;27:25–32PubMedCrossRefGoogle Scholar
  50. 50.
    Podo F. Tumor phospholipids metabolism. NMR Biomed. 1999;12:413–439PubMedCrossRefGoogle Scholar
  51. 51.
    Treglia G, Sadeghi R. Meta-analyses and systematic reviews on PET and PET/CT in oncology: the state of the art. Clin Transl Imaging. 2013;1:73–75CrossRefGoogle Scholar

Copyright information

© Asian Pacific Association for the Study of the Liver 2014

Authors and Affiliations

  • Francesco Bertagna
    • 1
    Email author
  • Mattia Bertoli
    • 1
  • Giovanni Bosio
    • 1
  • Giorgio Biasiotto
    • 2
  • Ramin Sadeghi
    • 3
  • Raffaele Giubbini
    • 1
  • Giorgio Treglia
    • 4
  1. 1.Nuclear MedicineUniversity of Brescia and Spedali Civili di BresciaBresciaItaly
  2. 2.Biomedical Technology DepartmentUniversity of BresciaBresciaItaly
  3. 3.Nuclear Medicine Research CenterMashhad University of Medical SciencesMashhadIran
  4. 4.Department of Nuclear Medicine and PET/CT CenterOncology Institute of Southern SwitzerlandBellinzonaSwitzerland

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