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

Abstract

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-¹³¹I-iodo-benzylguanidine (¹³¹I-MIBG) provides limited survival benefits and has adverse effects. A new generation of radionuclides for therapy using α-particles including meta-²¹¹At-astato-benzylguanidine (²¹¹At-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 ²¹¹At-MABG in a pheochromocytoma model. We evaluated tumor volume-reducing effects of ²¹¹At-MABG using rat pheochromocytoma cell line PC12 tumor-bearing mice. PC12 tumor-bearing mice received intravenous injections of ²¹¹At-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 ²¹¹At-MABG administration. The control group of ten mice received phosphate-buffered saline. The ²¹¹At-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 ²¹¹At-MABG showed only a temporary weight reduction, with recovery in weight by day 10. ²¹¹At-MABG exhibited a strong tumor volume-reducing effect in a mouse model of pheochromocytoma without weight reduction. Therefore, ²¹¹At-MABG might be an effective therapeutic agent for the treatment of malignant pheochromocytoma.