TY - JOUR
T1 - A new liposomal formulation of Gemcitabine is active in an orthotopic mouse model of pancreatic cancer accessible to bioluminescence imaging
AU - Bornmann, C.
AU - Graeser, R.
AU - Esser, N.
AU - Ziroli, V.
AU - Jantscheff, P.
AU - Keck, T.
AU - Unger, C.
AU - Hopt, U. T.
AU - Adam, U.
AU - Schaechtele, C.
AU - Massing, U.
AU - Von Dobschuetz, E.
N1 - Funding Information:
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.
PY - 2008/3
Y1 - 2008/3
N2 - 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.
AB - 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.
KW - Bioluminescence
KW - Gemcitabine
KW - Liposomes
KW - Orthotopic
KW - Pancreatic cancer
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UR - http://www.scopus.com/inward/citedby.url?scp=37249047522&partnerID=8YFLogxK
U2 - 10.1007/s00280-007-0482-z
DO - 10.1007/s00280-007-0482-z
M3 - Article
C2 - 17554540
AN - SCOPUS:37249047522
SN - 0344-5704
VL - 61
SP - 395
EP - 405
JO - Cancer Chemotherapy and Pharmacology
JF - Cancer Chemotherapy and Pharmacology
IS - 3
ER -