Facile method to radiolabel glycol chitosan nanoparticles with 64Cu via copper-free click chemistry for MicroPET imaging

Dong Eun Lee, Jin Hee Na, Sangmin Lee, Choong Mo Kang, Hun Nyun Kim, Seung Jin Han, Hyunjoon Kim, Yearn Seong Choe, Kyung Ho Jung, Kyo Chul Lee, Kuiwon Choi, Ick Chan Kwon, Seo Young Jeong, Kyung Han Lee, Kwangmeyung Kim

Research output: Contribution to journalArticlepeer-review

64 Scopus citations


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 64Cu 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 64Cu radionuclide. Following incubation with the 64Cu- radiolabeled DBCO complex (DBCO-PEG4-Lys-DOTA-64Cu with high specific activity, 18.5 GBq/μmol), the azide-functionalized CNPs were radiolabeled successfully with 64Cu, 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 64Cu-radiolabeled CNPs (64Cu-CNPs) did not show any significant effect on the physicochemical properties, such as size, zeta potential, or spherical morphology. After 64Cu-CNPs were intravenously administered to tumor-bearing mice, the real-time, in vivo biodistribution and tumor-targeting ability of 64Cu-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.

Original languageEnglish
Pages (from-to)2190-2198
Number of pages9
JournalMolecular Pharmaceutics
Issue number6
StatePublished - 3 Jun 2013


  • copper-free click chemistry
  • microPET imaging
  • nanoparticles
  • radiolabeling


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