Enhancement of survival of 9L gliosarcoma bearing rats following intracerebral delivery of drugs in combination with microbeam radiation therapy.
Microbeam radiation therapy (MRT) is a form of radiosurgery first dedicated to the treatment of brain tumors. It uses arrays of synchrotron generated X-rays microbeams of very high doses (typically 625 Gy). Microbeams are typically few micrometers large (25 microm) and few hundred micrometers spaced (200 microm). Previous experiments have shown that despite a good tumor eradication rate (5/11), a 100-microm spacing unidirectional irradiation (skin dose 625 Gy, width 25 microm) was too invasive for normal tissue. On the contrary, a 200-microm spacing unidirectional irradiation preserved healthy tissue with a low tumor eradication rate (2/32). The purpose of this study was to enhance the potential of the 200 microm spacing irradiation protocol. After diagnosis of the tumor by MRI, 9L tumor-bearing rats were laterally irradiated with 51 microbeams (625 Gy, 25 microm, 200 microm) 14 days after implantation. Three drugs (Gd-DTPA, CisPt, temozolomide) were tested, after intratumoral injection at the theoretical center of the tumor. Control rats displayed a median survival time of 19 days. There was no significant difference between drug-treated rats and control group. Irradiated animals showed an increase in life span (ILS) of 60.5%. Interestingly, the ILS increased to 131.6% and 1/6 rat survived more than 1 year in case of MRT combined with gadolinium injection. These results showed that the synergy between gadolinium injection (acting as a dose enhancer) and MRT improved significantly the life span of tumor bearing rats (more than a factor 2).
Régnard
Pierrick
P
Biomedical Facility, 6, Rue Jules Horowitz, ESRF, BP220, F 38043 Grenoble, France.
Bräuer-Krisch
Elke
E
Troprès
Irène
I
Keyriläinen
Jani
J
Bravin
Alberto
A
Le Duc
Géraldine
G
D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage; D001932:Brain Neoplasms / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D017024:Chemotherapy, Adjuvant; D003606:Dacarbazine / Q000031:analogs & derivatives; D018316:Gliosarcoma / Q000473:pathology / Q000628:therapy*; D015552:Injections, Intralesional; D008297:Male; D011882:Radiotherapy, High-Energy / Q000379:methods*; D051381:Rats; D011916:Rats, Inbred F344; D016019:Survival Analysis; D015996:Survival Rate; D017356:Synchrotrons; D000077204:Temozolomide; D016896:Treatment Outcome
D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine; D000077204:Temozolomide