Process development of [64Cu]Cu-ATSM: efficient stabilization and sterilization for therapeutic applications
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Hypoxia plays an important role in tumor prognosis. [64Cu]Cu-ATSM, a hypoxia-targeted radioactive agent, reportedly shows antitumor effect in vivo. For clinical application, [64Cu]Cu-ATSM must be manufactured at high concentrations to allow the administration of a therapeutic dose with safe intravenous bolus injection. Fifteen radical scavengers were tested to stabilize [64Cu]Cu-ATSM against radiolysis, and sodium l-ascorbate was selected. The optimal sterilization membrane filter was evaluated from polyvinylidene fluoride (PVDF), polyether sulfone, and mixed cellulose esters; PVDF showed the most efficient radiochemical yield after filtration. The proposed procedures can be used for the practical manufacturing of [64Cu]Cu-ATSM for therapeutic use.
Keywords[64Cu]Cu-ATSM Hypoxia Internal radiotherapy Process development Stabilization Sterilization
This study was supported by Japan Agency for Medical Research and Development (AMED) programs of “Practical Research for Innovative Cancer Control (18ck0106373h0002)”. We would like to thank Editage (www.editage.jp) for English language editing.
Compliance with ethical standards
Conflict of interest
HM and EK are employees of Nihon Medi-Physics Co., Ltd. All the other authors declare that they have no conflict of interests.
- 8.Lewis JS, McCarthy DW, McCarthy TJ, Fujibayashi Y, Welch MJ (1999) Evaluation of 64Cu-ATSM in vitro and in vivo in a hypoxic tumor model. J Nucl Med 40:177–183Google Scholar
- 10.Fujibayashi Y, Taniuchi H, Yonekura Y, Ohtani H, Konishi J, Yokoyama A (1997) Copper-62-ATSM: a new hypoxia imaging agent with high membrane permeability and low redox potential. J Nucl Med 38:1155–1160Google Scholar
- 15.Yoshii Y, Yoneda M, Ikawa M, Furukawa T, Kiyono Y, Mori T, Yoshii H, Oyama N, Okazawa H, Saga T, Fujibayashi Y (2012) Radiolabeled Cu-ATSM as a novel indicator of overreduced intracellular state due to mitochondrial dysfunction: studies with mitochondrial DNA-less rho0 cells and cybrids carrying MELAS mitochondrial DNA mutation. Nucl Med Biol 39:177–185CrossRefGoogle Scholar
- 20.Yoshii Y, Matsumoto H, Yoshimoto M, Zhang MR, Oe Y, Kurihara H, Narita Y, Jin ZH, Tsuji AB, Yoshinaga K, Fujibayashi Y, Higashi T (2018) Multiple administrations of 64Cu-ATSM as a novel therapeutic option for glioblastoma: a translational study using mice with xenografts. Transl Oncol 11:24–30CrossRefGoogle Scholar
- 24.Japanese Pharmaceutical Excipients Dictionary (2016) Yakuji Nippo Limited, TokyoGoogle Scholar
- 25.DaTscan Ioflupane I 123 Injection prescribing information (2011) GE Healthcare, Arlington Heights, USAGoogle Scholar
- 26.Amyvid Florbetapir F 18 Injection prescribing information (2012) Ely Lilly, Indianapolis, USAGoogle Scholar
- 27.Vizamyl Flutemetamol F 18 Injection prescribing information (2013) GE Healthcare, Arlington Heights, USAGoogle Scholar
- 29.U.S. department of Health and Human Services/National Toxicology Program; Report on Carcinogens, Fourteenth Edition. November 2016: Butylated Hydroxyanisole. CAS No. 25013-16-5Google Scholar