Antibody-guided three-step therapy for high grade glioma with yttrium-90 biotin

While the incidence of brain tumours seems to be increasing, median surviva l in patients with glioblastoma remains less than 1 year, despite improved diagnostic imaging and neurosurgical techniques, and innovations in treatme nt. We have developed an avidin-biotin pre-targeting approach fur deliverin g therapeutic radionuclides to gliomas, using anti-tenascin monoclonal anti bodies, which seems potentially effective for treating these tumours. We tr eated 48 eligible patients with histologically confirmed grade III or IV gl ioma and documented residual disease or recurrence after conventional treat ment. Three-step radionuclide therapy was performed by intravenous administ ration of 35 mg/m(2) of biotinylated anti-tenascin monoclonal antibody (Ist step), followed 36 h later by 30 mg of avidin and 50 mg of streptavidin (2 nd step), and 18-24 h later by 1-2 mg of yttrium-90-labelled biotin (3rd st ep). Y-90 doses of 2.22-2.96 GBq/m(2) were administered; maximum tolerated dose (MTD) was determined at 2.96 GBq/m(2). Tumour mass reduction (>25%-100 %), documented by computed tomography or magnetic resonance imaging, occurr ed in 12/48 patients (25%), with 8/48 having a duration of response of at l east 12 months. At present, 12 patients are still in remission, comprising four with a complete response, two with a parital response, two with a mino r response and four with stable disease. Median survival from Y-90 treatmen t is 11 months for grade IV glioblastoma and 19 months for grade III anapla stic gliomas. Avidin-biotin based three-step radionuclide therapy is well t olerated at the dose of 2.2 GBq/m(2), allowing the injection of Y-90-biotin without bone marrow transplantation. This new approach interferes with the progression of high-grade glioma and may produce tumour regression in pati ents no longer responsive to other therapies.