Bioinspired Synthesis of Intrinsically Radiolabeled Dy₂O₃ Nanoparticles as an In Vivo Generator of ¹⁶⁶Dy/¹⁶⁶Ho: A...

Functionalized inorganic nanoparticles (NPs) intrinsically radiolabeled with theranostic radiometals hold the potential to revolutionize cancer management. The appropriate choice of the radiometal used in the nanoplatform would not only aid in the diagnosis and staging of the disease but also facilitate them becoming an integral part of the therapeutic regimen, either as an independent treatment or in combination with other conventional modalities. Furthermore, due to the inherent characteristics of the NPs, such systems can demonstrate potential in multimodality imaging to offer improved diagnostic and therapeutic monitoring abilities for personalized treatment. In this study, intrinsically radiolabeled dysprosium oxide NPs were synthesized in a bioinspired manner for use as an efficient ¹⁶⁶Dy/¹⁶⁶Ho in vivo generator. The synthesized NPs (average size of 12.5 ± 2.4 nm) were extensively characterized by various instrumental techniques, including DLS, HRTEM, XRD, XPS, XANES, EXAFS, Raman spectroscopy, TGA, etc. Besides single-photon emission computed tomography (SPECT) imaging due to the nuclear decay characteristics of ¹⁶⁶Dy/¹⁶⁶Ho, the synthesized NPs demonstrated potential for use as contrast agents for magnetic resonance imaging (MRI) and computed tomography (CT) imaging, thereby combining three different imaging modalities in the same nanoplatform. In silico studies predicted the radiochemical stability and suitability of the intrinsically radiolabeled NPs for use as in vivo generator, which was further corroborated by SPECT imaging and biodistribution studies. Additionally, footpad administration of the intrinsically radiolabeled NPs led to clear visualization of the popliteal lymph node, highlighting their suitability for noninvasive sentinel lymph node mapping and for potential radiotherapy-based ablation of metastatic lymph nodes. Overall, this unique nanoplatform demonstrates promise for simultaneous diagnosis and therapy monitoring by multimodality (SPECT/MRI/CT) imaging along with precise cancer treatment.