Copper-64-alloyed gold nanoparticles for cancer imaging: Improved radiolabel stability and diagnostic accuracy

Gold nanoparticles, especially positron-emitter- labeled gold nanostructures, have gained steadily increasing attention in biomedical applications. Of the radionuclides used for nanoparticle positron emission tomography imaging, radiometals such as ⁶⁴Cu have been widely employed. Currently, radiolabeling through macrocyclic chelators is the most commonly used strategy. However, the radiolabel stability may be a limiting factor for further translational research. We report the integration of ⁶⁴Cu into the structures of gold nanoparticles. With this approach, the specific radioactivity of the alloyed gold nanoparticles could be freely and precisely controlled by the addition of the precursor ⁶⁴CuCl ₂ to afford sensitive detection. The direct incorporation of ⁶⁴Cu into the lattice of the gold nanoparticle structure ensured the radiolabel stability for accurate localization in vivo. The superior pharmacokinetic and positron emission tomography imaging capabilities demonstrate high passive tumor targeting and contrast ratios in a mouse breast cancer model, as well as the great potential of this unique alloyed nanostructure for preclinical and translational imaging. Copper goes for gold: Alloyed copper-gold nanoparticles with controlled integration of ⁶⁴Cu (⁶⁴CuAuNPs) are ideal for positron emission tomography imaging. The direct incorporation of ⁶⁴Cu into the lattice of gold nanoparticles ensured greatly improved radiolabel stability and detection sensitivity. The superior biodistribution profile and imaging capability demonstrated the potential of these alloyed nanoparticles for further investigation.