A Mouse Positron Emission Tomography Study of the Biodistribution of Gold Nanoparticles with Different Surface Coatings Using Embedded Copper-64

Anders Floor Frellsen, Anders Elias Hansen, Rasmus Irming Jølck, Paul Kempen, Gregory W Severin, Palle H Rasmussen, Andreas Kjær, Andreas Tue Ingemann Jensen, Thomas Lars Andresen

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By taking advantage of the ability of (64)Cu to bind non-specifically to gold surfaces, we have developed a new methodology to embed this radionuclide inside gold nanoparticles (AuNPs). (64)Cu enables the in vivo imaging of AuNPs by positron emission tomography (PET). AuNPs have a multitude of uses within health technology and are useful tools for general nanoparticle research. (64)Cu-AuNPs were prepared by incubating AuNP seeds with (64)Cu(2+), followed by the entrapment of the radionuclide by grafting a second layer of gold on the surface. This resulted in radiolabeling efficiencies of 53 ± 6%. The radiolabel showed excellent stability when challenging with EDTA for two days (>95% radioactivity retention) and showed no loss of (64)Cu when incubated with 50% mouse serum for two days. The methodology was chelator-free, and circumvents traditional concerns over chelator instability and altered AuNP properties due to surface modification. Radiolabeled (64)Cu-AuNP cores were prepared in a biomedically relevant size of 30 nm and used to investigate the in vivo stability of three different AuNP coatings by PET imaging in a murine xenograft tumor model. We found the longest plasma half-life (T½ = 9 hours) and highest tumor accumulation (3.9 %ID/g) by using polyethylene glycol (PEG) coating, while faster elimination from the bloodstream was observed with both a Tween 20-stabilized coating and a zwitterionic coating based on a mixture of sulfonic acids and quaternary amines, which has previously been reported to be superior to PEG. The new embedding method provides the utilization of PET imaging in combination with the multituide of uses that AuNPs have found in health technology, and the method can equally well be utilized for therapeutic copper radioisotopes for use in radiotherapy.
Original languageEnglish
JournalA C S Nano
Number of pages12
Publication statusPublished - 2016


  • Gold Nanoparticles
  • Copper-64
  • PET
  • Intrinsic Radiolabeling
  • Coating Materials

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