Pharmacokinetic evaluation of chelator-free radioactive copper gold alloy nanoparticle for cancer imaging

Objectives Radioactive Cu-64 labeled gold nanoparticles (AuNPs) have been widely used for oncological imaging. The conventional strategy is through the chelators, which raises the concern of radiolabeling stability and diagnostic accuracy. Herein, we developed a novel chelator-free approach to radiolabel the AuNPs by alloying 64Cu into the lattice of AuNPs for cancer PET imaging.

Methods The 64CuAuNPs in two sizes were synthesized in oleiyamine or aqueous buffer. The radiolabel stability of 64CuAuNPs was evaluated in PBS and mouse serum, respectively. In vivo pharmacokinetic evaluation of 64CuAuNPs was performed in wide-type mice. Passive targeting capability of 64CuAuNPs was studied in an EMT-6 mouse breast cancer model using a microPET/CT system.

Results The 64CuAuNPs were prepared in 27±3.2 nm and 4.3±0.2 nm characterized by dynamic light scattering, respectively. The specific activity of 64CuAuNPs was controlled by varying the amount of 64CuCl2 precursor. The stability studies showed no degradation or translation up to 48 h post injection (p.i.) in mouse serum. At 1 h p.i., the larger 64CuAuNPs showed much higher (p<0.001, n=4) blood circulation (45.4±2.5%ID/g) than the smaller counterpart (5.7±0.8%ID/g). However, at 24 h p.i., the smaller 64CuAuNPs had significantly lower (p<0.0001, n=4) uptake in the liver and spleen (14.6±2.7%ID/g and 2.1±0.5%ID/g, respectively) than the larger version (42.9±3.5 %ID/g in the liver and 203±11%ID/g in the spleen). Initial PET/CT imaging with the larger 64CuAuNPs showed effective tumor targeting (16.8±1.0 %ID/g) at 48 h p.i.

Conclusions The 64CuAuNPs demonstrated the new radiochemistry to make radioactive nanoparticle for cancer imaging. The stable radiolabeling and favorable pharmacokinetics in vivo make them candidate nanoprobes for cancer imaging. Future studies will focus on the targeted cancer imaging.

Research Support This work was supported in part by a start-up fund from Mallinckrodt Institute of Radiology, Washington University