HSA-coated intrinsically radiolabeled [177Lu]Lu₂O₃ nanoparticles for injectable nanoscale brachytherapy: Preclinical validation and first-in-human imaging.

Abstract

Localized radionuclide therapy can deliver high radiation doses to solid tumors while minimizing systemic exposure, but effective retention of therapeutic radionuclides at the tumor site remains challenging. We developed an injectable nanomedicine comprising human serum albumin (HSA)-coated intrinsically radiolabeled [177Lu]Lu₂O₃ nanoparticles for sustained intratumoral radiation delivery. The formulation was prepared using an albumin-mediated biomineralization approach and adapted for concentrated clinical-dose preparation without post-synthesis purification or concentration. In 4T1 tumor-bearing mice, 98.6 ± 1.2%, 97.9 ± 1.3%, and 96.5 ± 1.2% of administered activity remained in the tumor at 1, 4, and 24 h, respectively, with 88.2 ± 1.4% retained at 14 d. Free [177Lu]LuCl₃ showed rapid tumor clearance and systemic redistribution. Tumor absorbed dose was estimated at 27.5 Gy/MBq. Serial SPECT imaging in six patients with locally advanced breast cancer demonstrated tumor-localized radioactivity for up to 18 d with minimal distant redistribution. These findings support the feasibility of this platform for injectable nanoscale brachytherapy.

Abstract as supplied by the indexing source. © the authors / publisher.