Intralesional radioimmunotherapy of malignant gliomas. An effective treatment in recurrent tumors

Abstract

Background: Intralesional radioimmunotherapy (RAIT) may improve the management of malignant gliomas whose prognosis is, at present, very poor. Current treatment modalities (e.g., surgery, radiotherapy, and chemotherapy) may prolong survival by a few months but cannot prevent tumor recurrence.

Methods: Following one or more surgical operations, radiotherapy, and chemotherapy, 24 patients with recurrent malignant gliomas (23 brain and 1 spinal cord) underwent RAIT with 2 murine monoclonal antibodies (MoAb), BC-2 and BC-4, raised against tenascin (TN). This antigen is expressed in large amounts in the stroma of glial tumors but not normal brain tissue. The isotope used was iodine-131 (131I). The radiolabelled antibodies were injected directly into the tumor by means of a removable catheter or an indwelling catheter placed in the site of disease at the time of craniotomy. The patients were admitted to the protocol if histochemical analysis of their tumors demonstrated the presence of TN in high abundance. Biodistribution and dosimetry of an intralesional tracer dose (1 mg MoAb and 37 MBq 131I) were studied. RAIT was performed by the administration of escalating doses of radioiodine, ranging from 15 mCi to 57 mCi. In many cases, RAIT was was repeated two, three, or four times (on 8, 3 and 4 patients, respectively).

Results: Pharmacokinetic data resulted, on average, as follows: the 24-hour tumor/background ratio was 16.6; the percentage of injected dose concentrated per gram of tumor at 24 hours was 2.4%; and the effective half-life of the MoAb at the tumor was 74.5 hours. The mean radiation dose to the tumor was 36.48 cGy per MBq of 131I injected. Both systemic and brain toxicities were absent, while human anti-mouse antibody production after MoAb administration occurred in only a few cases. At present, 17 patients are assessable, with a median survival time of 16 months. Objective responses consisted of 5 tumor stabilizations (median time, 9 months), 3 partial remissions (11 months), and 3 complete remissions (15 months).