Glioblastoma therapy by direct intralesional administration of I-131 radioiodine labeled antitenascin antibodies

Abstract

Thirty patients with recurrent glioblastomas (29 brain, 1 spinal cord) received intralesional radioimmunotherapy aiming to control the progression of the tumor after surgery and radiotherapy. The BC-2 and/or BC-4 murine MAbs (Sorin-Biomedica, Saluggia, Italy) were utilized. They strongly react against tenascin (TN), which is an extracellular antigen expressed in large amounts by the stroma of glioblastoma but not by normal brain. The MAbs were labeled with I-131 and were injected directly into the tumor mass to maximize the antibody concentration in the tumor and to irradiate the neoplastic cells. The dose consisted, on average, of 3 mg antibody and 1100 MBq I-131. In most cases the radioimmunotherapy (RIT) applications were repeated two, three, or four times. No systemic adverse reactions were recorded. The brain tolerance to direct antibodies injection was quite good. The antibody concentration in the tumor was high and the MAb residence time in neoplastic tumor was prolonged. Consequently the mean radiation dose to the tumor was high: >25,000 cGy/cycle. Of 23 evaluable patients, we recorded 7 tumor stabilization (lasting, on mean, 9.1 mo), 4 partial remission (10 mo), and 4 complete remission (18 mo). The overall response rate was 34.7%.