title: Bioluminescence monitoring of intracranial glioblastoma xenograft: response to primary and salvage temozolomide therapy.
abstract: OBJECTIVE
  Bioluminescence imaging (BLI) offers a rapid and accurate means for longitudinal study of tumor cell growth and response to therapy in rodent models. Because this technology has only recently come into use in the field of small animal imaging, applications in this area have been limited. In the current study we have applied BLI to the analysis of clinically relevant issues involving use of the DNA methylating agent temozolomide (TMZ) in a mouse model.
  
  
  METHODS
  An invasive glioblastoma multiforme xenograft was modified for BLI via transduction with a luciferase-encoding lentivirus. Supratentorial tumors were established in athymic nude mice that were subsequently assigned randomly to control and TMZ treatment groups, and the extent of intracranial tumor was monitored using BLI.
  
  
  RESULTS
  In an experiment designed to compare the extent of antitumor effect between a single high-dose TMZ treatment and a protracted low-dose TMZ regimen, BLI revealed the protracted regimen as having superior antitumor effect, and this interpretation was consistent with results from a survival comparison between the two TMZ treatment groups. In a second experiment designed to assess the utility of BLI for testing therapies against recurrent glioblastoma multiforme, mice with intracranial tumors were retreated with TMZ at a time when BLI monitoring revealed tumor regrowth following initial TMZ treatment, and retreatment was successful in providing additional survival benefit.
  
  
  CONCLUSIONS
  The results of these experiments indicate that BLI monitoring can be used as a surrogate for predicting survival benefit from TMZ treatment, permits early determination of relative survival benefit associated with distinct TMZ therapeutic regimens, and offers a means of investigating secondary/salvage therapy efficacy following tumor regrowth from initial therapy.
authors: Neuroscience Graduate Program, Mayo Clinic, Rochester, Minnesota, USA.
authors: Eduard B
authors: EB
authors: Dinca
authors: Jann N
authors: JN
authors: Sarkaria
authors: Mark A
authors: MA
authors: Schroeder
authors: Brett L
authors: BL
authors: Carlson
authors: Ramona
authors: R
authors: Voicu
authors: Nalin
authors: N
authors: Gupta
authors: Mitchel S
authors: MS
authors: Berger
authors: C David
authors: CD
authors: James
mesh_terms: D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000473:pathology* / Q000503:physiopathology / Q000628:therapy; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004195:Disease Models, Animal; D005909:Glioblastoma / Q000473:pathology* / Q000503:physiopathology / Q000628:therapy; D049449:Luminescence; D049408:Luminescent Agents; D051379:Mice; D008819:Mice, Nude; D008991:Monitoring, Physiologic / Q000379:methods*; D016879:Salvage Therapy; D000077204:Temozolomide; D023041:Xenograft Model Antitumor Assays
chemical_list: D018906:Antineoplastic Agents, Alkylating; D049408:Luminescent Agents; D003606:Dacarbazine; D000077204:Temozolomide