title: High Yield Production and Radiochemical Isolation of Isotopically Pure Arsenic-72 and Novel Radioarsenic Labeling Strategies for the Development of Theranostic Radiopharmaceuticals.
abstract: 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 (72)Ge(m) discs in an irrigation-cooled target system allowing for the production of isotopically pure (72)As 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 (72)Ge 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.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Ellison
authors.forename: Todd E
authors.initials: TE
authors.lastname: Barnhart
authors.forename: Feng
authors.initials: F
authors.lastname: Chen
authors.forename: Hao
authors.initials: H
authors.lastname: Hong
authors.forename: Yin
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: TRACON Pharmaceuticals, Inc. , San Diego, California 92122, United States.
authors.forename: Charles P
authors.initials: CP
authors.lastname: Theuer
authors.affiliation: Carbone Cancer Center and Materials Science Program, University of Wisconsin , Madison, Wisconsin 53706, United States.
authors.forename: Weibo
authors.initials: W
authors.lastname: Cai
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Nickles
authors.forename: Onofre T
authors.initials: OT
authors.lastname: DeJesus
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000493:pharmacokinetics; D001151:Arsenic / Q000737:chemistry*; D017357:Cyclotrons; D005857:Germanium / Q000737:chemistry; D006801:Humans; D007553:Isotope Labeling / Q000379:methods; D007554:Isotopes / Q000737:chemistry; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry; D049268:Positron-Emission Tomography; D011854:Radiochemistry / Q000379:methods; D011868:Radioisotopes / Q000737:chemistry* / Q000302:isolation & purification; D019275:Radiopharmaceuticals / Q000737:chemistry*; D000068936:Theranostic Nanomedicine / Q000379:methods*; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal; D007554:Isotopes; D011868:Radioisotopes; D019275:Radiopharmaceuticals; D005857:Germanium; D001151:Arsenic; C579557:carotuximab