Chelator-Free Radiolabeling of Nanographene: Breaking the Stereotype of Chelation

Angew Chem Int Ed Engl. 2017 Mar 6;56(11):2889-2892. doi: 10.1002/anie.201610649. Epub 2017 Feb 7.


Macrocyclic chelators have been widely employed in the realm of nanoparticle-based positron emission tomography (PET) imaging, whereas its accuracy remains questionable. Here, we found that 64 Cu can be intrinsically labeled onto nanographene based on interactions between Cu and the π electrons of graphene without the need of chelator conjugation, providing a promising alternative radiolabeling approach that maintains the native in vivo pharmacokinetics of the nanoparticles. Due to abundant π bonds, reduced graphene oxide (RGO) exhibited significantly higher labeling efficiency in comparison with graphene oxide (GO) and exhibited excellent radiostability in vivo. More importantly, nonspecific attachment of 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) on nanographene was observed, which revealed that chelator-mediated nanoparticle-based PET imaging has its inherent drawbacks and can possibly lead to erroneous imaging results in vivo.

Keywords: graphene; imaging agents; nanoparticles; positron emission tomography; radiolabeling.

Publication types

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

MeSH terms

  • Animals
  • Breast Neoplasms / diagnostic imaging*
  • Chelating Agents / chemistry*
  • Copper / chemistry
  • Copper Radioisotopes / chemistry*
  • Female
  • Graphite / chemistry*
  • Mammary Neoplasms, Experimental / diagnostic imaging
  • Mice
  • Nanoparticles / chemistry*
  • Particle Size
  • Positron-Emission Tomography*


  • Chelating Agents
  • Copper Radioisotopes
  • Graphite
  • Copper