学術雑誌論文 Antitumor effects of radionuclide treatment using α-emitting meta-211At-astato-benzylguanidine in a PC12 pheochromocytoma model

大島, 康宏  ,  須藤, 仁美  ,  渡辺, 茂樹  ,  永津, 弘太郎  ,  辻, 厚至  ,  坂下, 哲哉  ,  伊藤, 陽一  ,  吉永, 恵一郎  ,  東, 達也  ,  石岡, 典子

45 ( 6 )  , pp.999 - 1010 , 2018-01 , Springer International Publishing AG
ISSN:1619-7070
内容記述
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. β-emitting radiopharmaceutical meta-131I-iodo-benzylguanidine (131I-MIBG) has limited survival benefits and adverse effects. A new generation of radionuclide therapy using α-particles including meta-211At-astatobenzylguanidine (211At-MABG) is expected to have strong therapeutic effects with minimal side effects. However, this possibility has not been evaluated in a pheochromocytoma animal model. We aimed to evaluate the therapeutic effects of α-emitter 211At-MABG on a pheochromocytoma model. Methods: We evaluated tumor volume-reduction effects of 211At-MABG using rat pheochromocytoma cell line PC12 tumor-bearing mice. PC12 tumor-bearing mice received 211At-MABG (0.28, 0.56, 1.11, 1.85, 3.70 and 5.55 MBq; n = 5 each group) intravenously. The tumor volume was evaluated until 8 weeks after 211At-MABG administration. Control group (n = 10) received phosphate buffered saline (PBS).Results: The single 211At-MABG therapy showed significantly lower relative tumor growth until 38 days compared to control [relative tumor volume, control: 509.2% ± 169.1% vs. 9.6% ± 5.5% (0.56 MBq) at day 21, p < 0.01]. In addition, the 211At-MABG treatment groups with 0.28, 0.56 and 1.11 MBq showed only temporary weight reduction, recovering weight loss at day 10.Conclusion: 211At-MABG exhibited a strong tumor volume-reduction effect in a pheochromocytoma mouse model without weight reduction. Therefore, 211At-MABG might be an effective therapeutic agent for the treatment of malignant pheochromocytoma.

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