DOI: 10.1007/s00259-017-3919-6Pages: 999-1010

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

1. National Institutes for Quantum and Radiological Science and Technology, Department of Radiation-Applied Biology Research, Quantum Beam Science Research Directorate

2. National Institutes for Quantum and Radiological Science and Technology, National Institute of Radiological Sciences, Department of Molecular Imaging and Theranostics

3. National Institutes for Quantum and Radiological Science and Technology, National Institute of Radiological Sciences, Department of Radiopharmaceuticals Development

4. Hokkaido University Graduate School of Medicine, Department of Biostatistics

5. National Institutes for Quantum and Radiological Science and Technology, National Institute of Radiological Sciences, Diagnostic and Therapeutic Nuclear Medicine

Correspondence to:
Keiichiro Yoshinaga
Tel: +81-43-206-3402
Email: yoshinaga.keiichiro@qst.go.jp

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Abstract

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-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.

Methods

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.

Results

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.

Conclusion

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.

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  • Accepted: Dec 20, 2017
  • Online: Jan 19, 2018

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