title: Facile method to radiolabel glycol chitosan nanoparticles with (64)Cu via copper-free click chemistry for MicroPET imaging.
abstract: An efficient and straightforward method for radiolabeling nanoparticles is urgently needed to understand the in vivo biodistribution of nanoparticles. Herein, we investigated a facile and highly efficient strategy to prepare radiolabeled glycol chitosan nanoparticles with (64)Cu via a strain-promoted azide-alkyne cycloaddition strategy, which is often referred to as click chemistry. First, the azide (N3) group, which allows for the preparation of radiolabeled nanoparticles by copper-free click chemistry, was incorporated to glycol chitosan nanoparticles (CNPs). Second, the strained cyclooctyne derivative, dibenzyl cyclooctyne (DBCO) conjugated with a 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) chelator, was synthesized for preparing the preradiolabeled alkyne complex with (64)Cu radionuclide. Following incubation with the (64)Cu-radiolabeled DBCO complex (DBCO-PEG4-Lys-DOTA-(64)Cu with high specific activity, 18.5 GBq/μmol), the azide-functionalized CNPs were radiolabeled successfully with (64)Cu, with a high radiolabeling efficiency and a high radiolabeling yield (>98%). Importantly, the radiolabeling of CNPs by copper-free click chemistry was accomplished within 30 min, with great efficiency in aqueous conditions. In addition, we found that the (64)Cu-radiolabeled CNPs ((64)Cu-CNPs) did not show any significant effect on the physicochemical properties, such as size, zeta potential, or spherical morphology. After (64)Cu-CNPs were intravenously administered to tumor-bearing mice, the real-time, in vivo biodistribution and tumor-targeting ability of (64)Cu-CNPs were quantitatively evaluated by microPET images of tumor-bearing mice. These results demonstrate the benefit of copper-free click chemistry as a facile, preradiolabeling approach to conveniently radiolabel nanoparticles for evaluating the real-time in vivo biodistribution of nanoparticles.
authors.affiliation: Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, 29 Geumgu-gil, Jeongeup, Jeonbuk 580-185, Republic of Korea.
authors.forename: Dong-Eun
authors.initials: DE
authors.lastname: Lee
authors.forename: Jin Hee
authors.initials: JH
authors.lastname: Na
authors.forename: Sangmin
authors.initials: S
authors.lastname: Lee
authors.forename: Choong Mo
authors.initials: CM
authors.lastname: Kang
authors.forename: Hun Nyun
authors.initials: HN
authors.lastname: Kim
authors.forename: Seung Jin
authors.initials: SJ
authors.lastname: Han
authors.forename: Hyunjoon
authors.initials: H
authors.lastname: Kim
authors.forename: Yearn Seong
authors.initials: YS
authors.lastname: Choe
authors.forename: Kyung-Ho
authors.initials: KH
authors.lastname: Jung
authors.forename: Kyo Chul
authors.initials: KC
authors.lastname: Lee
authors.forename: Kuiwon
authors.initials: K
authors.lastname: Choi
authors.forename: Ick Chan
authors.initials: IC
authors.lastname: Kwon
authors.forename: Seo Young
authors.initials: SY
authors.lastname: Jeong
authors.forename: Kyung-Han
authors.initials: KH
authors.lastname: Lee
authors.forename: Kwangmeyung
authors.initials: K
authors.lastname: Kim
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D048271:Chitosan / Q000737:chemistry*; D057930:Click Chemistry / Q000379:methods*; D003301:Copper Radioisotopes / Q000737:chemistry*; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry*
chemical_list: D003301:Copper Radioisotopes; C118638:glycol-chitosan; D048271:Chitosan