High Yield Production and Radiochemical Isolation of Isotopically Pure Arsenic-72 and Novel Radioarsenic Labeling Strategies for the Development of Theranostic Radiopharmaceuticals

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• 作者：Paul A. Ellison ; Todd E. Barnhart ; Feng Chen ; Hao Hong ; Yin Zhang ; Charles P. Theuer ; Weibo Cai ; Robert J. Nickles ; Onofre T. DeJesus
• 刊名：Bioconjugate Chemistry
• 出版年：2016
• 出版时间：January 20, 2016
• 年：2016
• 卷：27
• 期：1
• 页码：179-188
• 全文大小：442K
• ISSN：1520-4812

文摘

Radioisotopes of arsenic are of considerable interest to the field of nuclear medicine with unique nuclear and chemical properties making them well-suited for use in novel theranostic radiopharmaceuticals. However, progress must still be made in the production of isotopically pure radioarsenic and in its stable conjugation to biological targeting vectors. This work presents the production and irradiation of isotopically enriched ⁷²Ge_(m) discs in an irrigation-cooled target system allowing for the production of isotopically pure ⁷²As with capability on the order of 10 GBq. A radiochemical separation procedure isolated the reactive trivalent radioarsenic in a small volume buffered aqueous solution, while reclaiming ⁷²Ge target material. The direct thiol-labeling of a monoclonal antibody resulted in a conjugate exhibiting exceptionally poor in vivo stability in a mouse model. This prompted further investigations to alternative radioarsenic labeling strategies, including the labeling of the dithiol-containing chelator dihydrolipoic acid, and thiol-modified mesoporous silica nanoparticles (MSN-SH). Radioarsenic-labeled MSN-SH showed exceptional in vivo stability toward dearsenylation.