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

Ellison, Paul A.; Barnhart, Todd E.; Chen, Feng; Hong, Hao; Zhang, Yin; Theuer, Charles P.; Cai, Weibo; Nickles, Robert J.; DeJesus, Onofre T.

doi:10.1021/acs.bioconjchem.5b00592

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

Journal Article · Tue Dec 08 00:00:00 EST 2015 · Bioconjugate Chemistry

DOI:https://doi.org/10.1021/acs.bioconjchem.5b00592· OSTI ID:1467565

Ellison, Paul A. ^[1]; Barnhart, Todd E. ^[2]; Chen, Feng ^[2]; Hong, Hao ^[2]; Zhang, Yin ^[2]; Theuer, Charles P. ^[3]; Cai, Weibo ^[4]; Nickles, Robert J. ^[2]; DeJesus, Onofre T. ^[2]

Univ. of Wisconsin School of Medicine and Public Health, Madison, WI (United States); University of Wisconsin
Univ. of Wisconsin School of Medicine and Public Health, Madison, WI (United States)
TRACON Pharmaceuticals, Inc., San Diego, CA (United States)
Univ. of Wisconsin School of Medicine and Public Health, Madison, WI (United States); Univ. of Wisconsin, Madison, WI (United States)

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). In conclusion, radioarsenic-labeled MSN-SH showed exceptional in vivo stability toward dearsenylation.

View Accepted Manuscript (DOE)

Research Organization:: Univ. of Wisconsin, Madison, WI (United States)

Sponsoring Organization:: USDOE

Grant/Contract Number:: SC0005281; SC0008384

OSTI ID:: 1467565

Journal Information:: Bioconjugate Chemistry, Journal Name: Bioconjugate Chemistry Journal Issue: 1 Vol. 27; ISSN 1043-1802

Publisher:: American Chemical SocietyCopyright Statement

Country of Publication:: United States

Language:: English

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