In vivo uptake of [11C]choline does not correlate with cell proliferation in human prostate cancer

  • Anthonius J. Breeuwsma
  • Jan Pruim
  • Maud M. Jongen
  • Albert J. Suurmeijer
  • Wim Vaalburg
  • Rien J. Nijman
  • Igle J. de Jong
Original Article



Prostate cancer is the second leading cause of death from cancer among US men. Positron emission tomography (PET) with [11C]choline has been shown to be useful in the staging and detection of prostate cancer. The background of the increased uptake of choline in human prostate cancer is not completely understood. The aim of this study was to prospectively investigate the relationship between the [11C]choline uptake and the cell proliferation in human prostate cancer.


Prostate cancer tissue from 18 patients who had undergone a radical prostatectomy for histologically proven disease was studied. An [11C]choline PET scan was performed prior to surgery. Post-prostatectomy specimens were prepared and stained with the antibody MIB-1 for Ki-67, which depicts proliferation. Two independent observers counted the amount of stained nuclei per specimen.


Prostate cancer showed Ki-67 staining and high uptake of [11C]choline. Statistical analysis showed no significant correlation between [11C]choline uptake and Ki-67 staining (R=0.23; P=0.34). No significant relationships were found between the uptake of [11C]choline (SUV) and either preoperative PSA (R=0.14; P=0.55) or Gleason sum score (R=0.28; P=0.25).


In vivo uptake of [11C]choline does not correlate with cell proliferation in human prostate cancer as depicted by Ki-67. Our results suggest that a process other than proliferation is responsible for the uptake of [11C]choline in prostate cancer.


Choline Prostate cancer Ki-67 Cell proliferation PET 


  1. 1.
    Sarma AV, Schottenfeld D. Prostate cancer incidence, mortality, and survival trends in the United States: 1981–2001. Semin Urol Oncol 2002;20(1):3–9.CrossRefPubMedGoogle Scholar
  2. 2.
    Jemal A, Thomas A, Murray T, Thun M. Cancer statistics, 2002. CA Cancer J Clin 2002;52(1):23–47.PubMedGoogle Scholar
  3. 3.
    Purohit RS, Shinohara K, Meng MV, Carroll PR. Imaging clinically localized prostate cancer. Urol Clin North Am 2003;30(2):279–93.Google Scholar
  4. 4.
    Harisinghani MG, Barentsz J, Hahn PF, Deserno WM, Tabatabaei S, van de Kaa CH, et al. Noninvasive detection of clinically occult lymph-node metastases in prostate cancer. N Engl J Med 2003;3482(25):2491–9.CrossRefPubMedGoogle Scholar
  5. 5.
    de Jong IJ, Pruim J, Elsinga PH, Vaalburg W, Mensink HJ. Visualization of prostate cancer with 11C-choline positron emission tomography. Eur Urol 2002;42(1):18–23.CrossRefPubMedGoogle Scholar
  6. 6.
    Hara T, Kosaka N, Kishi H. PET imaging of prostate cancer using carbon-11-choline. J Nucl Med 1998;39(6):990–5.PubMedGoogle Scholar
  7. 7.
    Kotzerke J, Prang J, Neumaier B, Volkmer B, Guhlmann A, Kleinschmidt K, et al. Experience with carbon-11 choline positron emission tomography in prostate carcinoma. Eur J Nucl Med 2000;27(9):1415–9.CrossRefPubMedGoogle Scholar
  8. 8.
    Podo F. Tumour phospholipid metabolism. NMR Biomed 1999;12(7):413–39.CrossRefPubMedGoogle Scholar
  9. 9.
    Ramirez de Molina A, Rodriguez-Gonzalez A, Gutierrez R, Martinez-Pineiro L, Sanchez J, Bonilla F, et al. Overexpression of choline kinase is a frequent feature in human tumor-derived cell lines and in lung, prostate, and colorectal human cancers. Biochem Biophys Res Commun 2000;296(3):580–3.Google Scholar
  10. 10.
    Zheng QH, Gardner TA, Raikwar S, Kao C, Stone KL, Martinez TD, et al. [11C]Choline as a PET biomarker for assessment of prostate cancer tumor models. Bioorg Med Chem 2004;12(11):2887–93.Google Scholar
  11. 11.
    Gerdes J, Lemke H, Baisch H, Wacker HH, Schwab U, Stein H. Cell cycle analysis of a cell proliferation-associated human nuclear antigen defined by the monoclonal antibody Ki-67. J Immunol 1984;133(4):1710–15.Google Scholar
  12. 12.
    Montironi R, van der Kwast T, Boccon-Gibod L, Bono AV, Boccon-Gibod L. Handling and pathology reporting of radical prostatectomy specimens. Eur Urol 2003;44(6):626–36.Google Scholar
  13. 13.
    Shi SR, Key ME, Kalra KL. Antigen retrieval in formalin-fixed, paraffin-embedded tissues: an enhancement method for immunohistochemical staining based on microwave oven heating of tissue sections. J Histochem Cytochem 1991;39(6):741–8.Google Scholar
  14. 14.
    Koopal SA, Iglesias Coma M, Tiebosch AT, Suurmeijer AJ. Low-temperature heating overnight in tris-HCl buffer pH 9 is a good alternative for antigen retrieval in formalin-fixed paraffin-embedded tissue. Appl Immunohistochem 1998;6(4):228–33.Google Scholar
  15. 15.
    Kallakury BV, Sheehan CE, Rhee SJ, Fisher HA, Kaufman RP Jr, Rifkin MD, et al. The prognostic significance of proliferation-associated nucleolar protein p120 expression in prostate adenocarcinoma: a comparison with cyclins A and B1, Ki-67, proliferating cell nuclear antigen, and p34cdc2. Cancer 1999;85(7):1569–76.CrossRefPubMedGoogle Scholar
  16. 16.
    Hara T. 11C-choline and 2-deoxy-2-[18F]fluoro-D-glucose in tumor imaging with positron emission tomography. Mol Imaging Biol 2002;4(4):267–73.CrossRefPubMedGoogle Scholar
  17. 17.
    Sutinen E, Nurmi M, Roivainen A, Varpula M, Tolvanen T, Lehikoinen P, et al. Kinetics of [11C]choline uptake in prostate cancer: a PET study. Eur J Nucl Med Mol Imaging 2004;31(3):317–24.Google Scholar
  18. 18.
    Heerschap A, Jager GJ, van der Graaf M, Barentsz JO, de la Rosette JJ, Oosterhof GO, et al. In vivo proton MR spectroscopy reveals altered metabolite content in malignant prostate tissue. Anticancer Res 1997;17(3A):1455–60.Google Scholar
  19. 19.
    Brown GD, Osman S, Wilson HK, Aboagye E, Price PM, Luthra SK, et al. Metabolism of [11C-methlyl]choline in tumour bearing mice and synthesis and isolation of its catabolite [11C-methyl]betaine. J Labelled Cpd Radiopharm 2001;44(Suppl 1):s107–9.Google Scholar
  20. 20.
    Roivainen A, Forsback S, Gronroos T, Lehikoinen P, Kahkonen 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(1):25–32.Google Scholar
  21. 21.
    Munoz E, Gomez F, Paz JI, Casado I, Silva JM, Corcuera MT, et al. Ki-67 immunolabeling in pre-malignant lesions and carcinoma of the prostate. Histological correlation and prognostic evaluation. Eur J Histochem 2003;47(2):123–8.Google Scholar
  22. 22.
    Tamboli P, Amin MB, Schultz DS, Linden MD, Kubus J. Comparative analysis of the nuclear proliferative index (Ki-67) in benign prostate, prostatic intraepithelial neoplasia, and prostatic carcinoma. Mod Pathol 1996;9(10):1015–9.Google Scholar
  23. 23.
    Epstein JI. Pathologic assessment of the surgical specimen. Urol Clin North Am 2001;28(3):567–94.Google Scholar
  24. 24.
    Stricker HJ, Jay JK, Linden MD, Tamboli P, Amin MB. Determining prognosis of clinically localized prostate cancer by immunohistochemical detection of mutant p53. Urology 1996;47(3):366–9.Google Scholar
  25. 25.
    Uzoaru I, Rubenstein M, Mirochnik Y, Slobodskoy L, Shaw M, Guinan P. An evaluation of the markers p53 and Ki-67 for their predictive value in prostate cancer. J Surg Oncol 1998;67(1):33–7.Google Scholar
  26. 26.
    Li R, Heydon K, Hammond ME, Grignon DJ, Roach M III, Wolkov HB, et al. Ki-67 staining index predicts distant metastasis and survival in locally advanced prostate cancer treated with radiotherapy: an analysis of patients in radiation therapy oncology group protocol 86–10. Clin Cancer Res 2004;10(12 Pt 1):4118–24.Google Scholar
  27. 27.
    Pollack A, DeSilvio M, Khor LY, Li R, Al Saleem TI, Hammond ME, et al. Ki-67 staining is a strong predictor of distant metastasis and mortality for men with prostate cancer treated with radiotherapy plus androgen deprivation: Radiation Therapy Oncology Group trial 92–02. J Clin Oncol 2004;22(11):2133–40.Google Scholar
  28. 28.
    Oyama N, Akino H, Kanamaru H, Suzuki Y, Muramoto S, Yonekura Y, et al. 11C-acetate PET imaging of prostate cancer. J Nucl Med 2002;43(2):181–6.PubMedGoogle Scholar
  29. 29.
    Utriainen M, Komu M, Vuorinen V, Lehikoinen P, Sonninen P, Kurki T, et al. Evaluation of brain tumor metabolism with [11C]choline PET and 1H-MRS. J Neurooncol 2003;62(3):329–38.Google Scholar
  30. 30.
    Hara T, Kosaka N, Kishi H. Development of 18F-fluoroethylcholine for cancer imaging with PET: synthesis, biochemistry, and prostate cancer imaging. J Nucl Med 2002;43(2):187–99.PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Anthonius J. Breeuwsma
    • 1
    • 2
  • Jan Pruim
    • 2
  • Maud M. Jongen
    • 1
  • Albert J. Suurmeijer
    • 3
  • Wim Vaalburg
    • 2
  • Rien J. Nijman
    • 1
  • Igle J. de Jong
    • 1
  1. 1.Department of UrologyGroningen University HospitalGroningenThe Netherlands
  2. 2.PET CentreGroningen University HospitalGroningenThe Netherlands
  3. 3.Department of PathologyGroningen University HospitalGroningenThe Netherlands

Personalised recommendations