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A new liposomal formulation of Gemcitabine is active in an orthotopic mouse model of pancreatic cancer accessible to bioluminescence imaging

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Abstract

Despite its rapid enzymatic inactivation and therefore limited activity in vivo, Gemcitabine is the standard drug for pancreatic cancer treatment. To protect the drug, and achieve passive tumor targeting, we developed a liposomal formulation of Gemcitabine, GemLip (∅: 36 nm: 47% entrapment). Its anti-tumoral activity was tested on MIA PaCa-2 cells growing orthotopically in nude mice. Bioluminescence measurement mediated by the stable integration of the luciferase gene was employed to randomize the mice, and monitor tumor growth. GemLip (4 and 8 mg/kg), Gemcitabine (240 mg/kg), and empty liposomes (equivalent to 8 mg/kg GemLip) were injected intravenously once weekly for 5 weeks. GemLip (8 mg/kg) stopped tumor growth, as measured via in vivo bioluminescence, reducing the primary tumor size by 68% (SD ± 8%; p < 0.02), whereas Gemcitabine hardly affected tumor size (-7%; ± 1.5%). In 80% of animals, luciferase activity in the liver indicated the presence of metastases. All treatments, including the empty liposomes, reduced the metastatic burden. Thus, GemLip shows promising antitumoral activity in this model. Surprisingly, empty liposomes attenuate the spread of metastases similar to Gemcitabine and GemLip. Further, luciferase marked tumor cells are a powerful tool to observe tumor growth in vivo, and to detect and quantify metastases.

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Acknowledgment

We are extremely grateful to Marta Rodriguez-Franco and Gunter Neuhaus (Institute for Biology II; Cell Biology;University Freiburg) for the permission to use their CCD camera, and their lab-members for hosting us. Furthermore, we would like to thank Sandra Pöllath and Bianca Giesen for excellent technical assistance, and Lenka Taylor for critically reading the manuscript. This work was funded, in part, by grants from the Clotten Stiftung and Dietmar Hopp Stiftung GmbH.

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Authors and Affiliations

  1. Department of General and Visceral Surgery, Albert-Ludwigs-University Freiburg, Freiburg, Germany

    C. Bornmann, T. Keck, U. T. Hopt, U. Adam & E. von Dobschuetz

  2. ProQinase GmbH, Breisacher Strasse 117, 79106 , Freiburg, Germany

    R. Graeser, N. Esser & C. Schaechtele

  3. Tumor Biology Center, Freiburg, Germany

    V. Ziroli, P. Jantscheff, C. Unger & U. Massing

Authors
  1. C. Bornmann
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  2. R. Graeser
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  3. N. Esser
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  4. V. Ziroli
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  5. P. Jantscheff
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  6. T. Keck
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  7. C. Unger
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  8. U. T. Hopt
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  9. U. Adam
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  10. C. Schaechtele
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  11. U. Massing
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  12. E. von Dobschuetz
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Corresponding author

Correspondence to R. Graeser.

Additional information

C. Bornmann and R. Graeser have equally contributed to this article.

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Bornmann, C., Graeser, R., Esser, N. et al. A new liposomal formulation of Gemcitabine is active in an orthotopic mouse model of pancreatic cancer accessible to bioluminescence imaging. Cancer Chemother Pharmacol 61, 395–405 (2008). https://doi.org/10.1007/s00280-007-0482-z

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  • DOI: https://doi.org/10.1007/s00280-007-0482-z

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