title: Dosimetry and dose-response relationships in newly diagnosed patients with malignant gliomas treated with iodine-131-labeled anti-tenascin monoclonal antibody 81C6 therapy.
abstract: OBJECTIVE
  The objective of this study was to perform the dosimetry and evaluate the dose-response relationships in newly diagnosed patients with malignant brain tumors treated by direct injections of (131)I-labeled 81C6 monoclonal antibody (MAb) into surgically created resection cavities (SCRCs).
  
  
  METHODS
  Absorbed doses to the 2-cm-thick shell as measured from the margins of the resection cavity interface were estimated for 42 patients with primary brain tumors. MR images were used to assess the enhanced-rim volume as a function of time after radiolabeled MAb therapy. Biopsy samples were obtained from 15 patients and 1 autopsy.
  
  
  RESULTS
  The average absorbed dose [range] to the 2-cm shell region was 32 [3-59] Gy. For the endpoint of minimal time to MR contrast enhancement, the optimal absorbed dose and initial dose-rate were 43 +/- 16 Gy and 0. 41 +/- 0.10 Gy/h, respectively. There was a correlation between the absorbed dose and dose rate to the shell region and biopsy outcome (tumor recurrence, radionecrosis, and tumor recurrence and/or radionecrosis). In this Phase I study, the maximum tolerated dose (MTD) was 120 mCi. At this MTD, the estimated average absorbed dose and initial dose rate to the 2-cm shell were 41 [9-89] Gy and 0.51 [0.24-1.13] Gy/h, respectively. These values are in agreement with the optimal values based on the time to MR lesion rim enhancement.
  
  
  CONCLUSIONS
  The average absorbed dose to the 2-cm shell region varied considerably and mainly depended on cavity volume. In future clinical trials, the administered activity of (131)I-labeled 81C6 MAb may be adjusted based on cavity volume in order to deliver the optimal absorbed dose of 43 Gy rather than giving a fixed administered activity.
authors.affiliation: Department of Radiology, Duke University Medical Center, Durham, NC 27710, USA. akaba001@mc.duke.edu
authors.forename: G
authors.initials: G
authors.lastname: Akabani
authors.forename: I
authors.initials: I
authors.lastname: Cokgor
authors.forename: R E
authors.initials: RE
authors.lastname: Coleman
authors.forename: D
authors.initials: D
authors.lastname: González Trotter
authors.forename: T Z
authors.initials: TZ
authors.lastname: Wong
authors.forename: H S
authors.initials: HS
authors.lastname: Friedman
authors.forename: A H
authors.initials: AH
authors.lastname: Friedman
authors.forename: A
authors.initials: A
authors.lastname: Garcia-Turner
authors.forename: J E
authors.initials: JE
authors.lastname: Herndon
authors.forename: D
authors.initials: D
authors.lastname: DeLong
authors.forename: R E
authors.initials: RE
authors.lastname: McLendon
authors.forename: X G
authors.initials: XG
authors.lastname: Zhao
authors.forename: C N
authors.initials: CN
authors.lastname: Pegram
authors.forename: J M
authors.initials: JM
authors.lastname: Provenzale
authors.forename: D D
authors.initials: DD
authors.lastname: Bigner
authors.forename: M R
authors.initials: MR
authors.lastname: Zalutsky
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000532:radiotherapy*; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005910:Glioma / Q000532:radiotherapy*; D006801:Humans; D007457:Iodine Radioisotopes / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D016499:Radioimmunotherapy / Q000379:methods*; D019063:Tenascin / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D007457:Iodine Radioisotopes; D019063:Tenascin