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

By taking advantage of the ability of Cu-64 to bind nonspecifically to gold surfaces, we have developed a methodology to embed this radionuclide inside gold nanoparticles (AuNPs). Cu-64 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. Cu-64-AuNPs were prepared by incubating AuNP seeds with (64)4CU(2+), followed by the entrapment of the radionuclide by grafting on a second layer of gold. This resulted in radiolabeling efficiencies of 53 +/- 6%. The radiolabel showed excellent stability when incubated with EDTA for 2 days (95% radioactivity retention) and showed no loss of Cu-64 when incubated with 50% mouse serum for 2 days. The methodology was chelator-free, removing traditional concerns over chelator instability and altered AuNP properties due to surface modification. Radiolabeled Cu-64-AuNP cores were prepared in biomedically relevant sizes of 20-30 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 (T-1/2 about 9 h) and tumor accumulation (3.9%ID/g) to result from a polyethylene glycol 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. In the in vivo model, the Cu-64 was observed to closely follow the AuNPs for each coating, again attributed to the excellent stability of the radiolabel.