量子科学技術研究開発機構学術機関リポジトリ

Objectives
Pheochromocytoma is a known neuroendocrine tumor. Around 10% of pheochromocytomas are malignant and metastasize to bone, lung, etc. It is a refractory disease lacking an effective treatment. For malignant pheochromocytoma, treatment using with meta‐[131I]iodobenzylguanidine ([131I]MIBG) has been performed, but its therapeutic effect is limited. By applying α‐rays with a higher biological effect and shorter range than β‐rays to targeted radioisotope therapy, not only higher therapeutic effect can be expected but also radiation damage to normal tissues can be minimized. Therefore, meta‐[211At]astatobenzylguanidine ([211At]MABG) has been developed using astatine‐211 (211At, half‐life: 7.2 h), which emits α‐rays and has chemical properties similar to iodine.1 Its high accumulation in tumors and strong tumor volume‐reducing effect in pheochromocytoma model mice have already been reported.2 Currently, Our facility is planning to develop [211At]MABG for human clinical research in collaboration with the National Institutes for Quantum and Radiological Science and Technology (QST), which reported the therapeutic effect in mice. The aim is to synthesize [211At]MABG with a remotely controlled synthesizer using in‐house produced 211At at the Fukushima Medical University (FMU).
Methods
We produced 211At using 209Bi (α, 2n) 211At reaction by the MP‐30 cyclotron in FMU. The purification was carried out by dry distillation and obtained 211At as chloroform solution. An [211At]MABG‐remotely controlled synthesizer, designed and produced by the QST group, was installed in the glove box. 211At solution (13.5–141.4 MBq, ca. 0.1 mL) was introduced into the synthesizer and [211At]MABG was synthesized from the precursor, meta‐trimethylsilylbenzylguanidine hemisulfate (0.25 mg, 0.92 μmol) by electrophilic substitution reaction with N‐chlorosuccinimide (NCS, 50 μL as saturated solution in methanol) and trifluoroacetic acid (TFA, 0.35 mL) at 70°C for 10 min. Purification was carried out by solid phase extraction (Sep‐Pak tC18 Plus Light Cartridge, Waters). After washing with water (0.5 mL), [211At]MABG was eluted with 5% ethanol aqueous solution (2 mL). The quality of [211At]MABG was confirmed using radio‐HPLC.
Results
When [211At]MABG was synthesized using the synthesizer, the radiochemical yield was 59 ± 5%, and the synthesis time was 42 ± 2 minutes (n = 3). The maximum yield was 61.4 MBq (EOS). By solid‐phase extraction, it was possible to remove most of regents including NCS, precursor, and unreacted 211At. The radiochemical purity was >95%.
Conclusions
We succeeded in synthesizing [211At]MABG using 211At produced in FMU, and stable production was enabled in the yield and the synthesis time by using the synthesizer.
REFERENCES
Vaidyanathan G, Zalutsky MR. Bioconjug Chem 1992;3:499.
Ohshima Y, Sudo H, Watanabe S, Nagatsu K, Tsuji AB, Sakashita T, et al. Eur J Nucl Med Mol Imaging 2018; 45: 999–1010

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ISRS2019

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2019-05-30

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2023-05-15 18:47:38.688737

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Synthesis of [211At]MABG using remote‐controlled synthesizer and quality evaluation

× Aoki, Miho

× Minegishi, Katsuyuki

× Nishijima, Kenichi

× Suzuki, Hisashi

× Sasaki, Shigenori

× Washiyama, Kohshin

× Zhao, Songji

× Nagatsu, Kotaro

× Ming-Rong, Zhang

× Takahashi, Kazuhiro