Loco-regional radioimmunotherapy of high-grade malignant gliomas using specific monoclonal antibodies labeled with Y-90: A phase I study

A Phase I radioimmunotherapy trial was conducted in which radioconjugated m onoclonal antibody (MAb) was directly infused into the tumor or postoperati ve tumoral bed in patients with high-grade malignant glioma. BC-4, a murine MAb that recognizes tenascin, was used in these studies. The MAb was label ed with Y-90, a pure beta emitter with maximum energy of 2.284 MeV, which c an penetrate into tissue up to 0.5-0.7 cm. Stable Y-90-labeled MAb conjugat es were prepared using the chelator p-isothiocyanatobenzyl derivative of di ethylenetriaminepentaacetic acid (ITC-Bz-DTPA), obtaining >95% labeling eff iciency and conserving the antibodies' immunoreactivity (>85%). Twenty pati ents, 2 with anaplastic astrocytoma and 18 with glioblastoma, were included in the study. All of the patients had been treated previously with convent ional therapies (surgery, external radiotherapy, and chemotherapy) and pres ented with progressive disease not amenable to further treatment. A dose-es calation study was performed using doses ranging from 530 mCi (185-1110 MBq ) of Y-90-labeled MAb BC-4. The protein dose of MAb was always 1 mg. Three patients were treated at the 5, 10, 15, and 20 mCi levels, and the 25- and 30-mCi doses were each administered to 4 patients. Systemic toxicity was co mpletely absent in all of the patients. The maximum tolerated dose to the b rain was 25 mCi (925 MBq). The average dose to the tumor was 3200 cGy/mCi. Doses to the liver, bone marrow, and kidneys were below 10 cGy/mCi in all o f the cases. Biodistribution studies demonstrated that the Y-90-labeled MAb accreted exclusively in the neoplastic area without any diffusion into the normal brain or other normal organs. No clinical responses were recorded b ecause of the very advanced stage of disease at the time of radioimmunother apy.