Stable Radiolabeling of Sulfur-Functionalized Silica Nanoparticles with Copper-64

Nanoparticles labeled with tadiornetals enable whole-body nuclear imaging and therapy. Though chelating agents are commonly used to radiolabel biomolecules, nanoparticles offer the advantage of attaching a radiometal directly to the nanoparticle itself without the need, of such agents. We previously demonstrated that direct radiolabeling of silica nanoparticles with hard, oxophilic ions, such as the positron emitters zirconium-89 and gallium-68, is remarkably efficient. However, softer radiometals, such as the widely employed copper-64, do not stably bind to the silica matrix and quickly dissociate tinder physiological,conditions., Here; we overcome this limitation through the use of silica nanoparticles functionalized with a soft electron-donating thiol group to allow stable, attachment of copper-64. This approach significantly improves the stability of copper-64 labeled thiol, functionalized silica nanoparticles relative to native silica nanoparticles, thereby enabling in vivo PET imaging, and may be translated to other softer radiometals with affinity for sulfur. The presented approach expands the application, of silica nanoparticles as a platform for facile radiolabeling with both hard and soft radiometal ions.