title: Direct injection of 90Y MoAbs into glioma tumor resection cavities leads to limited diffusion of the radioimmunoconjugates into normal brain parenchyma: a model to estimate absorbed radiation dose.
abstract: OBJECTIVE
  Previously we have demonstrated that radioimmunoconjugates can be injected into glioma resection cavities to deliver a boost of radiation to the cavity edge with little toxicity to the normal brain. In the mathematical models we have previously published to assist in the development of this strategy we assumed that antibody remains associated with the cavity edge and no diffusion occurs. However, moderate diffusion might be beneficial while, if this were excessive, it would decrease the therapeutic index markedly.
  
  
  METHODS
  Selected individuals with relapsed malignant glioma underwent further surgical debulking; 90Y MoAb radioimmunotherapy; and open biopsy to determine the extent to which the conjugate diffuses from the cavity edge. Samples from these patients were taken in radial tracts and the corrected activity in each sample was plotted against distance from the cavity wall to determine appropriate diffusion constants.
  
  
  RESULTS
  Our data indicates that diffusion of radioimmunoconjugate from the edge of a glioma resection cavity appears to be an exponential process. The mean Ro for each patients data set ranged from 0.48-0.63 (overall mean 0.6) cm. A dosimetric model was developed that translates these measurements into estimates of radiation dose. Applying the clinical data to this model indicates that, in each patient, the peak dose is delivered 0.16-0.18 cm below the cavity margin, and the mean dose at 2 cm deep is 5.3% (4.4-5.8%) of the peak.
  
  
  CONCLUSIONS
  The model described can be used to translate diffusion constants measured by any method into estimates of absorbed radiation dose. Assuming similar diffusion kinetics, it can also be used to predict the dose deposited if alternative radionuclides are linked to MoAb, although the effect of dose rate should also be considered. In the future, it may be possible to manipulate diffusion by using either different antibodies or antibody fragments for intracavity radioimmunotherapy. Before this can be done, however, further data are needed and a noninvasive approach to measuring diffusion would clearly be optimal.
authors.affiliation: Paediatric and Neuro-Oncology Group, Frenchay Hospital, Bristol, UK.
authors.forename: K
authors.initials: K
authors.lastname: Hopkins
authors.forename: C
authors.initials: C
authors.lastname: Chandler
authors.forename: J
authors.initials: J
authors.lastname: Eatough
authors.forename: T
authors.initials: T
authors.lastname: Moss
authors.forename: J T
authors.initials: JT
authors.lastname: Kemshead
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001706:Biopsy; D001921:Brain / Q000473:pathology; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D003131:Combined Modality Therapy; D005910:Glioma / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D006801:Humans; D018796:Immunoconjugates / Q000008:administration & dosage* / Q000493:pharmacokinetics; D015552:Injections, Intralesional; D008954:Models, Biological; D009364:Neoplasm Recurrence, Local / Q000378:metabolism / Q000532:radiotherapy* / Q000601:surgery; D016499:Radioimmunotherapy / Q000379:methods*; D015021:Yttrium Radioisotopes / Q000008:administration & dosage* / Q000493:pharmacokinetics
chemical_list: D000911:Antibodies, Monoclonal; D018796:Immunoconjugates; D015021:Yttrium Radioisotopes