MO‐FG‐303‐08: PET‐Detectable Bimetallic (Zn@Au) Nanoparticles for Radiotherapy and Molecular Imaging Applications

Purpose: A technical challenge in clinical translation of GNP‐mediated radiotherapy is lack of in‐vivo imaging tools for monitoring biodistribution of GNPs. While several modalities (x‐ray fluorescence, photoacoustic, etc.) are investigated, we propose a potentially more effective technique based on PET imaging. We developed Zn@Au NPs whose Zn core acts as positron emitters when activated by protons, while the Au shell plays the original role for GNP‐mediated radiosensitization. Methods: Spherical Zn NPs (∼7nm diameter) were synthesized and then coated with ∼7nm thick Au layer to make Zn@Au NPs (∼20nm diameter). A water slurry containing 29mg of Zn@Au NPs was deposited (<10µm thickness) on a thin cellulose target and subsequently baked to remove the water. The cellulose matrix was placed in an aluminum target holder and irradiated with 14.5MeV protons from a GE PETtrace cyclotron with 4µA for 5min. After irradiation the cellulose matrix with the NPs was placed in a dose calibrator to assay radioactivity. Gamma spectroscopy using a HPGe detector was conducted on a very small fraction (<1mg) of the irradiated NPs. Results: We measured 158µCi of activity 32min after end of bombardment (EOB) using 66Ga setting on the dose calibrator (contribution from the cellulose matrix is negligible) which decreased to 2µCi over a 24hrs period. A gamma spectrum started one hour after EOB on the small fraction and acquired for 700sec showed a strong peak at 511keV (∼40,000 counts) with several other peaks (highest peak <1200 counts) of smaller magnitude. Conclusion: Strong 511keV gamma emission from proton‐activated Zn cores can potentially be utilized to image the biodistribution of Zn@Au NPs using a PET scanner. The developed Zn@Au NPs are expected to retain radiosensitizing capability similar to solid GNPs, while observable through PET imaging for human‐sized objects. Moreover, bioconjugated PET‐detectable GNPs would allow a new option to perform molecular imaging.