Antitumor effects of radionuclide treatment using α-emitting meta-(211)At-astato-benzylguanidine in a PC12 pheochromocytoma model

PURPOSE: Therapeutic options for patients with malignant pheochromocytoma are currently limited, and therefore new treatment approaches are being sought. Targeted radionuclide therapy provides tumor-specific systemic treatments. The β-emitting radiopharmaceutical meta-(131)I-iodo-benzylguanidine ((131)I-MIBG) provides limited survival benefits and has adverse effects. A new generation of radionuclides for therapy using α-particles including meta-(211)At-astato-benzylguanidine ((211)At-MABG) are expected to have strong therapeutic effects with minimal side effects. However, this possibility has not been evaluated in an animal model of pheochromocytoma. We aimed to evaluate the therapeutic effects of the α-emitter (211)At-MABG in a pheochromocytoma model. METHODS: We evaluated tumor volume-reducing effects of (211)At-MABG using rat pheochromocytoma cell line PC12 tumor-bearing mice. PC12 tumor-bearing mice received intravenous injections of (211)At-MABG (0.28, 0.56, 1.11, 1.85, 3.70 and 5.55 MBq; five mice per group). Tumor volumes were evaluated for 8 weeks after (211)At-MABG administration. The control group of ten mice received phosphate-buffered saline. RESULTS: The (211)At-MABG-treated mice showed significantly lower relative tumor growth during the first 38 days than the control mice. The relative tumor volumes on day 21 were 509.2% ± 169.1% in the control mice and 9.6% ± 5.5% in the mice receiving 0.56 MBq (p < 0.01). In addition, the mice treated with 0.28, 0.56 and 1.11 MBq of (211)At-MABG showed only a temporary weight reduction, with recovery in weight by day 10. CONCLUSION: (211)At-MABG exhibited a strong tumor volume-reducing effect in a mouse model of pheochromocytoma without weight reduction. Therefore, (211)At-MABG might be an effective therapeutic agent for the treatment of malignant pheochromocytoma. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00259-017-3919-6) contains supplementary material, which is available to authorized users.