177Lu-Labeled HEDP-Functionalized Manganese-Substituted Maghemite Nanocarriers for Localized Radionuclide Therapy

Background/Objectives: Effective intratumoral radionuclide therapy requires nanocarriers that enable stable radionuclide coordination and prolonged tumor retention. Integrating these properties with efficient magnetic heating within a single nanoplatform remains challenging because optimization of one property may compromise another. This study investigated whether manganese substitution could improve the magnetic heating performance of 1-hydroxyethylidene-1,1-diphosphonic acid (HEDP)-functionalized maghemite nanoparticles while preserving their suitability for radiopharmaceutical applications.

Methods

Three MnxFe2−xO3 compositions (x = 0, 0.221, and 0.480) were evaluated in terms of their structural and physicochemical properties, colloidal stability, and magnetic heating performance. The most promising Mn-substituted formulation and the unsubstituted reference were evaluated by 177Lu radiolabeling, in vitro radiochemical stability testing, whole-body imaging, ex vivo biodistribution analysis, and therapeutic efficacy assessment in 4T1 tumor-bearing mice.