title: A pilot study of the treatment of patients with recurrent malignant gliomas with intratumoral yttrium-90 radioimmunoconjugates.
abstract: A pilot study of the treatment of patients with relapsed malignant gliomas with direct intratumoral injections of yttrium-90 (90Y) radioimmunoconjugates has been completed. Patients were recruited following maximal tumour resection, and received 1-3 injections of 90Y conjugated to a monoclonal antibody designated ERIC-1, which binds the neural cell-adhesion molecule. Data were collected to establish clinical toxicity, pharmacokinetics and radiation doses to the cavity wall and critical body organs. Twenty-three injections were completed in 15 patients, with a mean injected activity of 675 MBq (range 399-921). Early toxicity manifested as cerebral oedema and was readily controlled with dexamethasone. Delayed myelosuppression was observed but no intervention was required. Pharmacokinetic analysis confirmed prolonged retention of isotope in the cavity with correspondingly low activity in the bloodstream. These data were translated into estimates of absorbed radiation dose using the Medical Internal Radiation Dosimetry (MIRD) scheme. Mean doses, and dose rates, to the wall of the cavity, i.e. 'tumour,' were very high in comparison to normal tissue doses, with a further advantage if targeting was achieved.
authors.affiliation: Imperial Cancer Research Fund, 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: Bullimore
authors.forename: D
authors.initials: D
authors.lastname: Sandeman
authors.forename: H
authors.initials: H
authors.lastname: Coakham
authors.forename: J T
authors.initials: JT
authors.lastname: Kemshead
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000954:Antigens, Surface / Q000276:immunology; D001853:Bone Marrow / Q000528:radiation effects; D001929:Brain Edema / Q000209:etiology / Q000517:prevention & control; D001932:Brain Neoplasms / Q000532:radiotherapy*; D015816:Cell Adhesion Molecules, Neuronal / Q000276:immunology; D002648:Child; D003907:Dexamethasone / Q000627:therapeutic use; D005240:Feasibility Studies; D005260:Female; D005910:Glioma / Q000532:radiotherapy*; D006801:Humans; D018796:Immunoconjugates / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015552:Injections, Intralesional; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000532:radiotherapy*; D010865:Pilot Projects; D016499:Radioimmunotherapy; D011879:Radiotherapy Dosage; D015021:Yttrium Radioisotopes / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*
chemical_list: D000954:Antigens, Surface; D015816:Cell Adhesion Molecules, Neuronal; D018796:Immunoconjugates; D015021:Yttrium Radioisotopes; D003907:Dexamethasone