title: Use of magnetic resonance imaging to assess blood-brain/blood-glioma barrier opening during conformal radiotherapy.
abstract: OBJECTIVE
  For chemotherapy to act synergistically and safely with radiation against high-grade gliomas, drugs must pass the endothelial junctions of the blood-tumor barrier (BTB) to reach all tumor cells, and should not pass the blood-brain barrier (BBB) to cause toxicity to normal brain. The objective of this study was to assess BBB/BTB status using magnetic resonance imaging (MRI) during a course of radiotherapy of high-grade gliomas.
  
  
  METHODS
  Sixteen patients with grade 3 or 4 supratentorial malignant glioma receiving conformal radiotherapy (RT) underwent contrast-enhanced MRI before, during, and after completion of RT. A gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) uptake index was analyzed with respect to the tumor and RT dose received.
  
  
  RESULTS
  In the nonenhanced tumor region, contrast uptake increased significantly after the receipt of approximately 10 Gy (P < .01), and reached a maximum after the receipt of approximately 30 Gy. In the initially contrast-enhanced tumor region, contrast uptake decreased over the course of RT and became significant after completion of RT in patients without progressive disease. The healthy brain showed only nonsignificant changes during and after irradiation.
  
  
  CONCLUSIONS
  Contrast MRI reveals increases in Gd-DTPA uptake in the initially nonenhanced tumor region but not in the remaining brain during the course of RT, suggesting opening of the BTB. This finding suggests that the effect of conformal radiation is more selective on the BTB than the BBB, and there may be a window extending from 1 week after the initiation of radiotherapy to 1 month after the completion of treatment during which a pharmaceutical agent has maximum access to high-grade gliomas.
authors.affiliation: Department of Radiation Oncology, University of Michigan, 1500 E Medical Center Dr, Rm B2C438, Box 0010, Ann Arbor, MI 48109-0010, USA. yuecao@med.umich.edu
authors.forename: Yue
authors.initials: Y
authors.lastname: Cao
authors.forename: Christina I
authors.initials: CI
authors.lastname: Tsien
authors.forename: Zhou
authors.initials: Z
authors.lastname: Shen
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Tatro
authors.forename: Randall
authors.initials: R
authors.lastname: Ten Haken
authors.forename: Marc L
authors.initials: ML
authors.lastname: Kessler
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Chenevert
authors.forename: Theodore S
authors.initials: TS
authors.lastname: Lawrence
mesh_terms: D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000493:pharmacokinetics / Q000627:therapeutic use; D001812:Blood-Brain Barrier; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D002266:Carboxymethylcellulose Sodium / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D003131:Combined Modality Therapy; D003287:Contrast Media; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D019583:Dose Fractionation, Radiation; D005260:Female; D019786:Gadolinium DTPA; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology* / Q000532:radiotherapy*; D006801:Humans; D007369:Interferon Inducers / Q000493:pharmacokinetics / Q000627:therapeutic use; D016014:Linear Models; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D011070:Poly I-C / Q000493:pharmacokinetics / Q000627:therapeutic use; D011107:Polylysine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D011879:Radiotherapy Dosage; D020266:Radiotherapy, Conformal; D016019:Survival Analysis; D000077204:Temozolomide; D016896:Treatment Outcome
chemical_list: D018906:Antineoplastic Agents, Alkylating; D003287:Contrast Media; D007369:Interferon Inducers; D011107:Polylysine; D003606:Dacarbazine; C019531:poly ICLC; D019786:Gadolinium DTPA; D002266:Carboxymethylcellulose Sodium; D011070:Poly I-C; D000077204:Temozolomide