Interest of liposomal doxorubicin as a radiosensitizer in malignant glioma xenografts.
Malignant glioma patients have a life expectancy reduced to about 15 months despite aggressive surgery, radiotherapy (RT), and chemotherapy. Doxorubicin has shown a marked cytotoxic effect against malignant glioma cells in vitro. The brain exposure to this drug is, however, hindered by the blood-brain barrier. Encapsulation of doxorubicin in liposomal carriers has been shown to reduce toxicities and to improve brain tumors exposure to doxorubicin. In this study, we evaluated the radiosensitizing properties of a nonpegylated liposomal doxorubicin (Myocet, MYO) on two subcutaneous (U87 and TCG4) and one intracranial (U87) malignant glioma models xenografted on nude mice. Doxorubicin biodistribution was assessed by a high-performance liquid chromatography method. Antitumor efficacy was investigated by tumor volume measurements and mice survival determination. We showed that (i) encapsulation of doxorubicin ensured a preferential deposition of doxorubicin in tumoral tissue in comparison with free doxorubicin; (ii) doxorubicin accumulated in both subcutaneous and intracranial tumors during repeated injections of MYO and this accumulation was linked to the potentiation of RT efficacy on two subcutaneous models; (iii) MYO was unable to improve the antitumoral efficacy of RT on an intracranial glioma model. Finally, this study emphasizes the importance of performing preclinical studies on models closer as possible of human tumors and localization to be more predictive of therapeutic effects observed in humans.
Labussière
Marianne
M
EA 4001 Radiopotentialisation: de la préclinique à la clinique, Faculté de Médecine, Nancy Université, 9 avenue de la Forêt de Haye-BP 184, Vandoeuvre-les-Nancy, Nancy, France.
Aarnink
Alice
A
Pinel
Sophie
S
Taillandier
Luc
L
Escanyé
Jean-Marie
JM
Barberi-Heyob
Muriel
M
Bernier-Chastagner
Valérie
V
Plénat
François
F
Chastagner
Pascal
P
D000818:Animals; D001932:Brain Neoplasms / Q000532:radiotherapy; D004317:Doxorubicin / Q000627:therapeutic use*; D005260:Female; D005910:Glioma / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D051379:Mice; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use*; D012878:Skin Neoplasms / Q000532:radiotherapy; D023041:Xenograft Model Antitumor Assays
D011838:Radiation-Sensitizing Agents; D004317:Doxorubicin