Nuclear Medicine and Biology
Volume 33, Issue 6 , Pages 715-722 , August 2006

A 99mTc-labeled gemcitabine bisphosphonate drug conjugate as a probe to assess the potential for targeted chemotherapy of metastatic bone cancer

  • Amal A. El-Mabhouh

      Affiliations

    • Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta T6G 2N8, Canada
    • ,
  • Christo A. Angelov

      Affiliations

    • Department of Chemistry, University of Alberta, Edmonton, Alberta T6G 2G2, Canada
    • ,
  • Ron Cavell

      Affiliations

    • Department of Chemistry, University of Alberta, Edmonton, Alberta T6G 2G2, Canada
    • ,
  • John R. Mercer

      Affiliations

    • Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta T6G 2N8, Canada
    • Faculty of Medicine, Oncologic Imaging, Cross Cancer Institute, Edmonton, Alberta T6G 1Z2, Canada
    • Corresponding Author InformationCorresponding author. Faculty of Medicine, Oncologic Imaging, Cross Cancer Institute, Edmonton, Alberta, Canada T6G 1Z2. Tel.: +1 780 989 4312; fax: +1 780 432 8483.

Received 12 January 2006 ,Revised 14 June 2006 ,Accepted 15 June 2006.

References 

  1. Canadian Cancer Society/National Cancer Institute of Canada: Canadian Cancer Statistics 2005, Toronto, Canada, 2005. http://www.cancer.ca/vgn/images/portal/cit_86751114/48/28/401594768cw_2005stats_en.pdf.
  2. Ferlay J, Bray F, Pisani P, Parkin DM. GLOBOCAN 2000: cancer incidence, mortality and prevalence worldwide, version 1.0. IARC CancerBase No. 5. Lyon: IARC Press; 2001;
  3. Coleman RE. Metastatic bone disease: clinical features, pathophysiology and treatment strategies. Cancer Treat Rev. 2001;27:165–176
  4. Lake DE, Hudis CA. High-dose chemotherapy in breast cancer. Drugs. 2004;64:1851–1860
  5. Fleisch H. Bisphosphonates: mechanisms of action. Endocrinol Rev. 1998;19:80–100
  6. Uludag H, Yang J. Targeting systemically administered proteins to bone by bisphosphonate conjugation. Biotechnol Prog. 2002;18:604–611
  7. El-Mabhouh A, Angelov C, McEwan A, Jia G, Mercer J. Preclinical investigations of drug and radionuclide conjugates of bisphosphonates for the treatment of metastatic bone cancer. Cancer Biotherap Radiopharm. 2004;19:627–640
  8. El-Mabhouh , Mercer J. 188Re-labeled bisphosphonates as potential bifunctional agents for therapy in patients with bone metastases. Appl Radiat Isot. 2005;62:541–549
  9. Barton-Burke M. Gemcitabine: a pharmacologic and clinical overview. Cancer Nurs. 1999;22:176–183
  10. Kantoci D, Denike JK, Wechter WJ. Synthesis of aminobisphosphonates. Synth Comm. 1996;26:2037–2042
  11. Veerman G, Ruiz van Haperen VW, Vermorken JB, Noordhuis P, Braakhuis BJ, Pinedo HM, et al. Antitumor activity of prolonged as compared with bolus administration of 2′,2′-difluorodeoxycytidine in vivo against murine colon tumors. Cancer Chemother Pharmacol. 1996;38:335–342
  12. Boven E, Schipper H, Erkelens CAM, Hatty SA, Pinedo HM. The influence of the schedule and the dose of gemcitabine on the anti-tumor efficacy in experimental human cancer. Br J Cancer. 1993;68:52–56
  13. Braakhuis BJM, Ruiz van Haperen VWT, Boven E, Veerman G, Peters GJ. Schedule dependent antitumor effect of gemcitabine in in vivo model systems. Semin Oncol. 1995;22(Suppl 11):42–46
  14. Schultz RM, Merriman RL, Toth JE, Zimmermann JE, Hertel LW, Andis SL, et al. Evaluation of new anticancer agents against the MIA PaCa-2 and PANC-1 human pancreatic carcinoma xenografts. Oncol Res. 1993;5:223–228
  15. Hays MT, Berman M. Pertechnetate distribution in man after intravenous infusion: a compartmental model. J Nucl Med. 1977;18:898–904
  16. Hosain F, Spencer RP, Couthon HM, Sturtz GL. Targeted delivery of antineoplastic agent to bone: biodistribution studies of technetium-99m-labeled gem–bisphosphonate conjugate of methotrexate. J Nucl Med. 1996;37:105–107
  17. Arteaga-de-Murphy C, Melendez-Alafort L, Montoya-Molina CE, Sepulveda-Mendez J. Radiopharmacokinetic data for 99mTc-ABP: a new radiopharmaceutical for bone scanning: comparison with 99mTc-MDP. Nucl Med Biol. 1997;24:27–33
  18. Laznicek M, Laznickova A, Budsky F. 99Tcm-DTPMP as a skeletal scintigraphy agent: distribution in rats in comparison with 99Tcm-MDP. Nucl Med Commun. 1996;17:1016–1020
  19. Kanishi D. 99mTc-MDP accumulation mechanisms in bone. Oral Surg Oral Med Oral Pathol. 1993;75:239–246
  20. Okamoto Y. Accumulation of technetium-99m methylene diphosphonate: conditions affecting absorption to hydroxyapatite. Oral Surg Oral Med Oral Pathol. 1995;80:115–119
  21. Szeto CC, Chow KM. Nephrotoxicity related to new therapeutic compounds. Ren Fail. 2005;27:329–333
  22. Hirschberg R. Nephrotoxicity of third-generation intravenous bisphosphonates. Toxicology. 2004;196:165–167
  23. Barri YM, Munshi NC, Sukumalchantra S, Abulezz SR, Bonsib SM, Wallach J, et al. Podocyte injury associated glomerulopathies induced by pamidronate. Kidney Int. 2004;65:634–641
  24. Markowitz GS, Appel GB, Fine PL, Funvez AZ, Loon NR, Jagannath S, et al. Collapsing focal segmental glomerulosclerosis following treatment with high-dose pamidronate. J Am Soc Nephrol. 2001;12:1164–1172
  25. Shipley LA, Brown TJ, Cornpropst JD, Hamilton M, Daniels WD, Culp HW. Metabolism and disposition of gemcitabine, and oncolytic deoxycytidine analog, in mice, rats, and dogs. Drug Metab Dispos. 1992;20:849–855
  26. Buesa JM, Losa R, Fernandez A, Sierra M, Esteban E, Diaz A, et al. Phase I clinical trial of fixed-dose rate infusional gemcitabine and dacarbazine in the treatment of advanced soft tissue sarcoma, with assessment of gemcitabine triphosphate accumulation. Cancer. 2004;15(101):2261–2269

PII: S0969-8051(06)00105-3

doi: 10.1016/j.nucmedbio.2006.06.004

Nuclear Medicine and Biology
Volume 33, Issue 6 , Pages 715-722 , August 2006

Article Tools

* Image Usage & Resolution