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Clinical Experience with -Particle–Emitting ²¹¹At: Treatment of Recurrent Brain Tumor Patients with ²¹¹At-Labeled Chimeric Antitenascin Monoclonal Antibody 81C6

¹ Department of Radiology, Duke University Medical Center, Durham, North Carolina; ² The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, North Carolina; ³ Department of Medicine, Duke University Medical Center, Durham, North Carolina; ⁴ Department of Surgery, Duke University Medical Center, Durham, North Carolina; and ⁵ Department of Pathology, Duke University Medical Center, Durham, North Carolina

Correspondence: For correspondence or reprints contact: Michael R. Zalutsky, PhD, Department of Radiology, Box 3808, Duke University Medical Center, Durham, NC 27710. E-mail: zalut001{at}mc.duke.edu

-Particle–emitting radionuclides, such as ²¹¹At, with a 7.2-h half-life, may be optimally suited for the molecularly targeted radiotherapy of strategically sensitive tumor sites, such as those in the central nervous system. Because of the much shorter range and more potent cytotoxicity of -particles than of β-particles, ²¹¹At-labeled agents may be ideal for the eradication of tumor cells remaining after surgical debulking of malignant brain tumors. The main goal of this study was to investigate the feasibility and safety of this approach in patients with recurrent malignant brain tumors. Methods: Chimeric antitenascin monoclonal antibody 81C6 (ch81C6) (10 mg) was labeled with 71–347 MBq of ²¹¹At by use of N-succinimidyl 3-[²¹¹At]astatobenzoate. Eighteen patients were treated with ²¹¹At-labeled ch81C6 (²¹¹At-ch81C6) administered into a surgically created resection cavity (SCRC) and then with salvage chemotherapy. Serial -camera imaging and blood sampling over 24 h were performed. Results: A total of 96.7% ± 3.6% (mean ± SD) of ²¹¹At decays occurred in the SCRC, and the mean blood-pool percentage injected dose was 0.3. No patient experienced dose-limiting toxicity, and the maximum tolerated dose was not identified. Six patients experienced grade 2 neurotoxicity within 6 wk of ²¹¹At-ch81C6 administration; this neurotoxicity resolved fully in all but 1 patient. No toxicities of grade 3 or higher were attributable to the treatment. No patient required repeat surgery for radionecrosis. The median survival times for all patients, those with glioblastoma multiforme, and those with anaplastic astrocytoma or oligodendroglioma were 54, 52, and 116 wk, respectively. Conclusion: This study provides proof of concept for regional targeted radiotherapy with ²¹¹At-labeled molecules in oncology. Specifically, the regional administration of ²¹¹At-ch81C6 is feasible, safe, and associated with a promising antitumor benefit in patients with malignant central nervous system tumors.

Key Words: ²¹¹At • glioma • radioimmunotherapy • monoclonal antibodies • -particle therapy

COPYRIGHT © 2008 by the Society of Nuclear Medicine, Inc.

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