Cation Exchange Protocol to Radiolabel Rare-Earth Nanoparticles with Yttrium-90 for Radiotherapy and for Magnetic Resonance Imaging
来源：ACS Publications
Internal radiation therapy (iRT) is an emerging therapeutic approach based on high-energy radionuclide implants categorized as alpha or beta particles placed directly into the tumor to induce cancer cell damage. This work focuses on the development of a unique approach for incorporating β-emitter yttrium-90 (90Y) radionuclides via a cation exchange method into lanthanide-based nanoparticles (NPs), consisting of NaLnF4 composition (Ln = Gd, Lu). The proposed method, thanks to the principle of cation exchange, is a straightforward protocol that involves just the mixing of water-stabilized NPs and radionuclides in aqueous environments at room temperature and, upon a short incubation time, enables the exchange of Gd or Lu ions with 90Y with high efficiency. The radiotherapeutic effect of cation-exchanged NaLnF4:90Y is here proven on glioblastoma cell lines with significant cytotoxicity, with the NaLnF4:90Y NPs, while no intrinsic cytotoxicity was seen for nonradiolabeled NPs at the same material dose. Moreover, in the case of NaGdF4 NPs, the gadolinium ions functioning as a T1 contrast agents for magnetic resonance imaging (MRI) enables to track the cation exchange protocol by MR signal enhancement during the ion incorporation: indeed, the Y3+ replacement with Gd enables the release of Gd3+, which enhances the water exposure of Gd ions and, in turn, the enhancement of the T1 MRI signal.
we have developed a simple and efficient cation exchange (CE)-based radiolabeling method suitable for the straightforward radioloading of NaLnF4 NPs (Ln = either Gd or Lu) with 90Y radionuclide. This method allows for the rapid incorporation of 90Y under ambient conditions with high yields while also achieving high specific activity labeling, outperforming other radiolabeling techniques. Besides setting the conditions for the quick 90Y insertion with the most efficient purification protocol, in the case of NaGdF4 NPs compositions, we could also monitor the cation exchange reaction by MRI imaging and T1 signal, following the MRI brightness and an increase in the R1 signal of the released Gd3+ upon exchange. This hallmark work represents the first example and proof of concept of a CE method applied to rare-earth-based NPs as a tool for radioinsertion of pure β– emitters into tiny NPs to be used for iRT to be applied to the radiotherapy treatment of glioblastoma cells.