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Dosimetry and Radiographic Analysis of ¹³¹I-Labeled Anti–Tenascin 81C6 Murine Monoclonal Antibody in Newly Diagnosed Patients with Malignant Gliomas: A Phase II Study

¹ Department of Radiology, Duke University Medical Center, Durham, North Carolina
² Department of Medicine, Duke University Medical Center, Durham, North Carolina
³ Department of Surgery, Duke University Medical Center, Durham, North Carolina
⁴ Department of Pathology, Duke University Medical Center, Durham, North Carolina

The objective was to perform dosimetry and evaluate dose–response relationships in newly diagnosed patients with malignant brain tumors treated with direct injections of ¹³¹I-labeled anti–tenascin murine 81C6 monoclonal antibody (mAb) into surgically created resection cavities (SCRCs) followed by conventional external-beam radiotherapy and chemotherapy. Methods: Absorbed doses to the 2-cm-thick shell, measured from the margins of the resection cavity interface, were estimated for 33 patients with primary brain tumors. MRI/SPECT registrations were used to assess the distribution of the radiolabeled mAb in brain parenchyma. Results from biopsies obtained from 15 patients were classified as tumor, radionecrosis, or tumor and radionecrosis, and these were correlated with absorbed dose and dose rate. Also, MRI/PET registrations were used to assess radiographic progression among patients. Results: This therapeutic strategy yielded a median survival of 86 and 79 wk for all patients and glioblastoma multiforme (GBM) patients, respectively. The average SCRC residence time of ¹³¹I-mu81C6 mAb was 76 h (range, 34–169 h). The average absorbed dose to the 2-cm cavity margins was 48 Gy (range, 25–116 Gy) for all patients and 51 Gy (range, 27–116 Gy) for GBM patients. In MRI/SPECT registrations, we observed a preferential distribution of ¹³¹I-mu81C6 mAb through regions of vasogenic edema. An analysis of the relationship between the absorbed dose and dose rate and the first biopsy results yielded a most favorable absorbed dose of 44 Gy. A correlation between decreased survival and irreversible neurotoxicity was noted. A comparative analysis, in terms of median survival, was performed with previous brachytherapy clinical studies, which showed a proportional relationship between the average boost absorbed dose and the median survival. Conclusion: This study shows that ¹³¹I-mu81C6 mAb increases the median survival of GBM patients. An optimal absorbed dose of 44 Gy to the 2-cm cavity margins is suggested to reduce the incidence of neurologic toxicity. Further clinical studies are warranted to determine the effectiveness of ¹³¹I-mu81C6 mAb based on a target dose of 44 Gy rather than a fixed administered activity.

Key Words: radioimmunotherapy • tenascin-C • gliomas • brain tumors • dosimetry

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