Radioactive 198Au-Doped Nanostructures with Different Shapes for In Vivo Analyses of Their Biodistribution Tumor Uptake and Intratumoral Distribution

摘要

With Au nanocages as an example, we recently demonstrated that radioactive ¹⁹⁸Au could be incorporated into the crystal lattice of Au nanostructures for simple and reliable quantification of their in vivo biodistribution by measuring the γ radiation from ¹⁹⁸Au decay and for optical imaging by detecting the Cerenkov radiation. Here we extend the capability of this strategy to synthesize radioactive ¹⁹⁸Au nanostructures with a similar size but different shapes and then compare their biodistribution, tumor uptake, and intratumoral distribution using a murine EMT6 breast cancer model. Specifically, we investigated Au nanospheres, nanodisks, nanorods, and cubic nanocages. After PEGylation, an aqueous suspension of the radioactive Au nanostructures was injected into a tumor-bearing mouse intravenously, and their biodistribution was measured from the γ radiation while their tumor uptake was directly imaged using the Cerenkov radiation. Significantly higher tumor uptake was observed for the Au nanospheres and nanodisks relative to the Au nanorods and nanocages at 24 h postinjection. Furthermore, autoradiographic imaging was performed on thin slices of the tumor after excision to resolve the intratumoral distributions of the nanostructures. While both the Au nanospheres and nanodisks were only observed on the surfaces of the tumors, the Au nanorods and nanocages were distributed throughout the tumors.