PHARMACOKINETICS AND DOSE ESTIMATES FOLLOWING INTRATHECAL ADMINISTRATION OF I-131 MONOCLONAL-ANTIBODIES FOR THE TREATMENT OF CENTRAL-NERVOUS-SYSTEM MALIGNANCIES

Purpose: Treatment of malignant disease in the central nervous system (CNS) with systemic radiolabeled monoclonal antibodies (MoAbs) is comp romised by poor penetration into the cerebrospinal fluid (CSF), limite d diffusion into solid tumors, and the generation of anti-mouse antibo dies. To attempt to avoid these problems we have treated patients with diffuse neoplastic meningitis with radioimmunoconjugates injected dir ectly into the intrathecal space. Methods and Materials: Tumor-specifi c MoAbs were conjugated to Iodine-131 (I-131) (629-3331 MBq) by the Io dogen technique, and administered via an intraventricular reservoir. A clinical response rate of approximately 33% was achieved, with better results in more radiosensitive tumors, Here, we present detailed phar macodynamic data on patients receiving this intracompartmental targete d therapy. Results: Elimination from the ventricular CSF appeared biph asic, with more rapid clearance occurring in the first 24 h, Radioimmu noconjugate entered the subarachnoid space and subsequently the vascul ar compartment. From this information, the areas under the effective a ctivity curves for ventricular CSF, blood, and subarachnoid CSF were c alculated to permit dosimetry. Critical organ doses were calculated us ing conventional medical internal radiation dose (MIRD) formalism, Whe re available, S-values were taken from standard tables, To calculate t he doses to CSF, brain, and spinal cord, S-values were evaluated using the models described in the text. Conclusion: A marked advantage coul d be demonstrated for the dose delivered to tumor cells within the CSF as compared to other neural elements.