64Cu Core-labeled nanoparticles with high specific activity via metal-free click chemistry

ACS Nano. 2012 Jun 26;6(6):5209-19. doi: 10.1021/nn300974s. Epub 2012 May 8.


A novel strategy based on metal-free "click" chemistry was developed for the copper-64 radiolabeling of the core in shell-cross-linked nanoparticles (SCK-NPs). Compared with Cu(I)-catalyzed click chemistry, this metal-free strategy provides the following advantages for Cu-64 labeling of the core of SCK-NPs: (1) elimination of copper exchange between nonradioactive Cu in the catalyst and DOTA-chelated Cu-64; (2) elimination of the internal click reactions between the azide and acetylene groups in the same NPs; and (3) increased efficiency of the click reaction because water-soluble Cu(I) does not need to reach the hydrophobic core of the NPs. When 50 mCi Cu-64 was used for the radiolabeling, the specific activity of the radiolabeled product was 975 Ci/μmol at the end of synthesis, which represents the attachment of ca. 500 Cu-64 atoms per SCK-NP, giving in essence a 500-fold amplification of specific activity of the NP over that of the Cu-64 chelate. To the best of our knowledge, this is the highest specific activity obtained for Cu-64-labeled nanoparticles.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Copper / chemistry*
  • Crystallization / methods
  • Macromolecular Substances / chemistry
  • Materials Testing
  • Metal Nanoparticles / chemistry*
  • Metal Nanoparticles / ultrastructure*
  • Molecular Conformation
  • Nanoparticles / chemistry*
  • Nanoparticles / ultrastructure*
  • Particle Size
  • Surface Properties


  • Macromolecular Substances
  • Copper