Improved X-ray absorption capability of Core-shell nano-transducer in situ enhances γ-ray-excited radioluminescence imaging in vivo

Abstract Background Radioluminescence imaging (RLI) using nanoscintillators offers great potential for biomedical applications, yet remains constrained by low quantum efficiency and the reliance of Cerenkov imaging on high-energy radionuclides. The rational design of core-shell nano-transducers overcomes these constraints by enhancing X-ray absorption and energy confinement, thereby enabling efficient γ-ray excited radioluminescence. Results We engineered NaGdF₄:15%Eu@NaLuF₄ core-shell nanoparticles as a superior nano-scintillator, designed to leverage Technetium-99m (99mTc) as an ideal excitation source. The key advantage of our system lies in its ability to efficiently convert the low-energy electron emissions from 99mTc into intense radioluminescence, completely bypassing the Cerenkov threshold and thus overcoming the key limitations of Cerenkov radiation. The optimized core-shell structure exhibited a radioluminescence intensity slope (k1) of 10.9 × 104 (p/s/cm2/sr)/MBq under 99mTc excitation, representing a 110% enhancement over the core-only nanoparticles. This enhanced scintillation output was paired with a remarkable CT contrast slope (k₂) of 47.6 HU/(mg/mL), demonstrating superior X-ray absorption capability. Capitalizing on these attributes, when integrated with 99mTc-sulfur colloid, this platform enabled background-free, multimodal SPECT/CT/RLI for high-contrast sentinel lymph node mapping and precise image-guided resection in murine models, the success of which was conclusively confirmed by histology. Conclusion This work presents a progressive optimization of lanthanide-based nanoparticles (LnNPs) scintillators, unveiling their structure-dependent radioluminescence properties for enhanced output efficiency. It thereby provides key insights into energy transfer processes within core-shell architectures and fundamentally expands the repertoire of applicable radionuclides for optical imaging. Graphical Abstract