Chelator-free nanoparticles for intrinsic radiolabeling can be used for whole-body imaging and therapeutic applications. Several reports have demonstrated the principle of intrinsic radiolabeling. However, the work done to date has suffered from much of the same specificity issues as conventional molecular chelators, insofar as there is no singular nanoparticle substrate that has proven effective in binding a library of radiosotopes. We demonstrate that amorphous silica nanoparticles serve as general substrates for chelator-free radiolabeling and demonstrate their ability to bind six medically relevant isotopes of various oxidation states with high radiochemical yield. The stability of the binding to the silica correlates well with the hardness of the radioisotope, which validates our postulate that oxophylic radiometal ions bind to the oxygens on the surface. Thus hard, oxophilic ions, such as the positron emitters zirconium-89 and gallium-68, are remarkably estable in vivo stability. 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. However, softer radiometals, such as the widely employed copper-64, do not stably bind to the silica matrix and quickly dissociate under physiological conditions. This limitation is overcome via 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 thiolfunctionalized 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.

Chelator-free radiolabeling of nanoparticles

255th National Meeting (2018)

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