Specificity of the anti-glycolytic activity of 3-bromopyruvate confirmed by FDG uptake in a rat model of breast cancer

  • Manon Buijs
  • Josephina A. Vossen
  • Jean-Francois H. Geschwind
  • Takayoshi Ishimori
  • James M. Engles
  • Obele Acha-Ngwodo
  • Richard L. Wahl
  • Mustafa Vali


Purpose: To evaluate the anti-glycolytic effects of 3-BrPA on rats bearing RMT mammary tumors, by determining FDG uptake after intravenous administration of the therapeutic dose. Materials and Methods: Sixteen rats bearing RMT tumors were treated either with 15 mM 3-BrPA in 2.5 ml of PBS or with 2.5 ml of PBS. After treatment, all rats received FDG and were sacrificed 1 h later. Results: 3-BrPA treatment significantly decreased FDG uptake in tumors by 77% (p = 0.002). FDG uptake did not significantly decrease in normal tissues after treatment. Conclusion: Our study showed that 3-BrPA exhibits a strong anti-glycolytic effect on RMT cells implanted in rats.


Breast cancer 3-Bromopyruvate FDG RMT Animal model 


  1. 1.
    Jemal A, Siegel R, Ward E et al (2008) Cancer statistics, 2008. CA Cancer J Clin 58:71–96PubMedCrossRefGoogle Scholar
  2. 2.
    Dumitrescu RG, Cotarla I (2005) Understanding breast cancer risk—where do we stand in 2005? J Cell Mol Med 9:208–221PubMedCrossRefGoogle Scholar
  3. 3.
    Louwman MW, Vriezen M, van Beek MW et al (2007) Uncommon breast tumors in perspective: incidence, treatment and survival in The Netherlands. Int J Cancer 121:127–135PubMedCrossRefGoogle Scholar
  4. 4.
    Elias D, Pietroantonio DD (2006) Surgery for liver metastases from breast cancer. HPB Oxf 8:97–99Google Scholar
  5. 5.
    Perez EA (1999) Current management of metastatic breast cancer. Semin Oncol 26:1–10PubMedGoogle Scholar
  6. 6.
    Anderson DM, Rolnick SJ, Jackson J, Amundson J, Asche SE, Loes LM (2007) Impact of chemotherapy in women with metastatic breast cancer diagnosed 1990–2003. Clin Breast Cancer 7:801–803PubMedCrossRefGoogle Scholar
  7. 7.
    Rabbani SA, Mazar AP (2007) Evaluating distant metastases in breast cancer: from biology to outcomes. Cancer Metastasis Rev 26:663–674PubMedCrossRefGoogle Scholar
  8. 8.
    Trotti A, Colevas AD, Setser A et al (2003) CTCAE v3.0: development of a comprehensive grading system for the adverse effects of cancer treatment. Semin Radiat Oncol 13:176–181PubMedCrossRefGoogle Scholar
  9. 9.
    Geschwind JF, Georgiades CS, Ko YH, Pedersen PL (2004) Recently elucidated energy catabolism pathways provide opportunities for novel treatments in hepatocellular carcinoma. Expert Rev Anticancer Ther 4:449–457PubMedCrossRefGoogle Scholar
  10. 10.
    Isidoro A, Casado E, Redondo A et al (2005) Breast carcinomas fulfill the Warburg hypothesis and provide metabolic markers of cancer prognosis. Carcinogenesis 26:2095–2104PubMedCrossRefGoogle Scholar
  11. 11.
    Shin SW, Han H, Choo SW et al (2006) Hepatic intra-arterial injection of 3-bromopyruvate in rabbit VX2 tumor. Acta Radiol 47:1036–1041PubMedCrossRefGoogle Scholar
  12. 12.
    Vali M, Liapi E, Kowalski J et al (2007) Intraarterial therapy with a new potent inhibitor of tumor metabolism (3-bromopyruvate): identification of therapeutic dose and method of injection in an animal model of liver cancer. J Vasc Interv Radiol 18:95–101PubMedCrossRefGoogle Scholar
  13. 13.
    Ko YH, Pedersen PL, Geschwind JF (2001) Glucose catabolism in the rabbit VX2 tumor model for liver cancer: characterization and targeting hexokinase. Cancer Lett 173:83–91PubMedCrossRefGoogle Scholar
  14. 14.
    Xu RH, Pelicano H, Zhou Y et al (2005) Inhibition of glycolysis in cancer cells: a novel strategy to overcome drug resistance associated with mitochondrial respiratory defect and hypoxia. Cancer Res 65:613–621PubMedCrossRefGoogle Scholar
  15. 15.
    Kim W, Yoon JH, Jeong JM et al (2007) Apoptosis-inducing antitumor efficacy of hexokinase II inhibitor in hepatocellular carcinoma. Mol Cancer Ther 6:2554–2562PubMedCrossRefGoogle Scholar
  16. 16.
    Tatsumi M, Cohade C, Mourtzikos KA, Fishman EK, Wahl RL (2006) Initial experience with FDG-PET/CT in the evaluation of breast cancer. Eur J Nucl Med Mol Imaging 33:254–262PubMedCrossRefGoogle Scholar
  17. 17.
    Delbeke D (1999) Oncological applications of FDG PET imaging. J Nucl Med 40:1706–1715PubMedGoogle Scholar
  18. 18.
    Ethier SP, Cundiff KC (1987) Importance of extended growth potential and growth factor independence on in vivo neoplastic potential of primary rat mammary carcinoma cells. Cancer Res 47:5316–5322PubMedGoogle Scholar
  19. 19.
    Wahl RL, Henry CA, Ethier SP (1992) Serum glucose: effects on tumor and normal tissue accumulation of 2-[F-18]-fluoro-2-deoxy-D-glucose in rodents with mammary carcinoma. Radiology 183:643–647PubMedGoogle Scholar
  20. 20.
    Margolis DJ, Hoffman JM, Herfkens RJ, Jeffrey RB, Quon A, Gambhir SS (2007) Molecular imaging techniques in body imaging. Radiology 245:333–356PubMedCrossRefGoogle Scholar
  21. 21.
    Avril N, Menzel M, Dose J et al (2001) Glucose metabolism of breast cancer assessed by 18F-FDG PET: histologic and immunohistochemical tissue analysis. J Nucl Med 42:9–16PubMedGoogle Scholar
  22. 22.
    Endo K, Oriuchi N, Higuchi T et al (2006) PET and PET/CT using 18F-FDG in the diagnosis and management of cancer patients. Int J Clin Oncol 11:286–296PubMedCrossRefGoogle Scholar
  23. 23.
    Pantaleo MA, Nannini M, Maleddu A et al (2008) Conventional and novel PET tracers for imaging in oncology in the era of molecular therapy. Cancer Treat Rev 34:103–121PubMedCrossRefGoogle Scholar
  24. 24.
    Minn H, Kangas L, Knuutila V, Paul R, Sipila H (1991) Determination of 2-fluoro-2-deoxy-D-glucose uptake and ATP level for evaluating drug effects in neoplastic cells. Res Exp Med (Berl) 191:27–35CrossRefGoogle Scholar
  25. 25.
    Yamada K, Brink I, Bisse E, Epting T, Engelhardt R (2005) Factors influencing [F-18] 2-fluoro-2-deoxy-D-glucose (F-18 FDG) uptake in melanoma cells: the role of proliferation rate, viability, glucose transporter expression and hexokinase activity. J Dermatol 32:316–334PubMedGoogle Scholar
  26. 26.
    Geschwind JF, Ko YH, Torbenson MS, Magee C, Pedersen PL (2002) Novel therapy for liver cancer: direct intraarterial injection of a potent inhibitor of ATP production. Cancer Res 62:3909–3913PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Manon Buijs
    • 1
  • Josephina A. Vossen
    • 1
  • Jean-Francois H. Geschwind
    • 1
  • Takayoshi Ishimori
    • 1
  • James M. Engles
    • 1
  • Obele Acha-Ngwodo
    • 1
  • Richard L. Wahl
    • 1
  • Mustafa Vali
    • 1
  1. 1.Russell H. Morgan Department of Radiology, and Radiological SciencesDivision of Vascular and Interventional RadiologyBaltimoreUSA

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