title: An image guided small animal radiation therapy platform (SmART) to monitor glioblastoma progression and therapy response.
abstract: OBJECTIVE
  Glioblastoma multiforme is the most common malignant brain tumor. Standard treatment including surgery, radiotherapy and chemotherapy with temozolomide is not curative. There is a great need for in vitro and in vivo models closely mimicking clinical practice to ensure better translation of novel preclinical findings.
  
  
  METHODS
  A 3D spheroid model was established using the U87MG cell line. The efficacy of temozolomide, RT and combinations was assessed using growth delay assays. Orthotopic glioblastoma tumors were established, different radiation doses delivered based on micro-CT based treatment planning (SmART-plan) and dose volume histograms (DVH) were determined. Tumor growth was monitored using bioluminescent imaging.
  
  
  RESULTS
  3D spheroid cultures showed a dose-dependent growth delay upon single and combination treatments. Precise uniform radiation was achieved in all in vivo treatment groups at all doses tested, and DVHs showed accurate dose coverage in the planning target volume which resulted in tumor growth delay.
  
  
  CONCLUSIONS
  We demonstrate that 3D spheroid technology can be reliably used for treatment efficacy evaluation and that mimicking a clinical setting is also possible in small animals. Both these in vitro and in vivo techniques can be combined for clinically relevant testing of novel drugs combined with radiation.
authors.affiliation: Department of Radiotherapy (MAASTRO)/GROW - School for Developmental Biology & Oncology, Maastricht University, The Netherlands.
authors.forename: Sanaz
authors.initials: S
authors.lastname: Yahyanejad
authors.affiliation: Department of Radiotherapy (MAASTRO)/GROW - School for Developmental Biology & Oncology, Maastricht University, The Netherlands.
authors.forename: Stefan J
authors.initials: SJ
authors.lastname: van Hoof
authors.affiliation: Department of Radiotherapy (MAASTRO)/GROW - School for Developmental Biology & Oncology, Maastricht University, The Netherlands.
authors.forename: Jan
authors.initials: J
authors.lastname: Theys
authors.affiliation: Department of Radiotherapy (MAASTRO)/GROW - School for Developmental Biology & Oncology, Maastricht University, The Netherlands.
authors.forename: Lydie M O
authors.initials: LM
authors.lastname: Barbeau
authors.affiliation: Department of Oncology, London Health Sciences Center, Canada.
authors.forename: Patrick V
authors.initials: PV
authors.lastname: Granton
authors.affiliation: Department of Radiotherapy (MAASTRO)/GROW - School for Developmental Biology & Oncology, Maastricht University, The Netherlands.
authors.forename: Kim
authors.initials: K
authors.lastname: Paesmans
authors.affiliation: Department of Radiotherapy (MAASTRO)/GROW - School for Developmental Biology & Oncology, Maastricht University, The Netherlands.
authors.forename: Frank
authors.initials: F
authors.lastname: Verhaegen
authors.affiliation: Department of Radiotherapy (MAASTRO)/GROW - School for Developmental Biology & Oncology, Maastricht University, The Netherlands. Electronic address: marc.vooijs@maastrichtuniversity.nl.
authors.forename: Marc
authors.initials: M
authors.lastname: Vooijs
mesh_terms: D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology*; D001932:Brain Neoplasms / Q000628:therapy*; D045744:Cell Line, Tumor; D059248:Chemoradiotherapy / Q000379:methods*; D003131:Combined Modality Therapy; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D018450:Disease Progression; D005909:Glioblastoma / Q000628:therapy*; D016513:Mice, SCID; D011879:Radiotherapy Dosage; D011880:Radiotherapy Planning, Computer-Assisted / Q000379:methods; D020266:Radiotherapy, Conformal / Q000379:methods; D061089:Radiotherapy, Image-Guided / Q000379:methods; D018874:Spheroids, Cellular; D000077204:Temozolomide
chemical_list: D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine; D000077204:Temozolomide
keywords: 3D model; Glioblastoma; Image guided; Micro-CT; Small animal radiation; Temozolomide