In biomedical imaging, nanoparticles combined with radionuclides that generate Cerenkov luminescence are used in diagnostic imaging, photon-induced therapies and as activatable probes. In these applications, the nanoparticle is often viewed as a carrier inert to ionizing radiation from the radionuclide. However, certain phenomena such as enhanced nanoparticle luminescence and generation of reactive oxygen species cannot be completely explained by Cerenkov luminescence interactions with nanoparticles. Herein, we report methods to examine the mechanisms of nanoparticle excitation by radionuclides, including interactions with Cerenkov luminescence, β particles and γ radiation. We demonstrate that β-scintillation contributes appreciably to excitation and reactivity in certain nanoparticle systems, and that excitation by radionuclides of nanoparticles composed of large atomic number atoms generates X-rays, enabling multiplexed imaging through single photon emission computed tomography. These findings demonstrate practical optical imaging and therapy using radionuclides with emission energies below the Cerenkov threshold, thereby expanding the list of applicable radionuclides.
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We thank BTG Interventional Medicine for the supply of Theraspheres required to conduct the in vivo imaging. The Australian Nuclear Science and Technology Organization (ANSTO) is acknowledged for their generous provision of a research-grade gallium-68 generator and purification system along with the MSKCC nuclear pharmacy for 18FDG. We thank the MSKCC Radiochemistry and Molecular Imaging Probes Core for technical assistance with the Ge detector, P. Zanzonico and V. Longo of the Small Animal Imaging Core for their direction and assistance on the NanoSPECT/CT and medical physics discussions. This work was supported by the following grants: National Institutes of Health (NIH) R01EB014944 and R01CA183953 (to J.G.), T32 CA196585 (to T.M.S.), and National Science Foundation Integrative Graduate Education and Research Traineeship grant (DGS 0965983, at Hunter College). Technical services provided by the MSKCC Small-Animal Imaging Core Facility, supported in part by NIH Centre Grant number P30 CA08748, are gratefully acknowledged. NIH Shared Instrumentation Grant number 1 S10 RR028889-01, which provided funding support for the purchase of the NanoSPECT/CT Plus, and a Shared Resources Grant from the MSKCC Metastasis Research Centre, which provided funding support for the purchase of the IVIS Spectrum, are also gratefully acknowledged.
E.C.P., T.M.S. and J.G. have filed an international patent application regarding the content of the manuscript (PCT/US2016/018502).
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Pratt, E.C., Shaffer, T.M., Zhang, Q. et al. Nanoparticles as multimodal photon transducers of ionizing radiation. Nature Nanotech 13, 418–426 (2018). https://doi.org/10.1038/s41565-018-0086-2
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