Synthesis, characterization and evaluation of [169Yb]Yb-labeled tailored hydroxyapatite nanospheres for potential application in nanobrachytherapy.

BACKGROUND: The introduction of radiolabeled nanoparticles in the realm of brachytherapy has led to a promising therapeutic strategy for cancer management called 'nanobrachytherapy'. In the quest of developing a potent radiolabeled inorganic biomaterial for use in nanobrachytherapy, we report the synthesis and evaluation of 169Yb [T1/2 = 32.02 d]-labeled glucuronic acid (GA) functionalised hydroxyapatite (HA) nanoparticles (GAHAnp) and established its potency in pre-clinical settings. METHODS: GAHAnp having average hydrodynamic diameter of 45 ± 3 nm was synthesized and characterized using various analytical methods. Ytterbium-169 was produced with adequate radionuclidic purity by direct neutron activation of isotopically enriched Yb-target in research reactor. Radiolabeling protocol of GAHAnp with 169Yb to obtain [169Yb]Yb-GAHAnp in high yield and purity was optimized. Adsorption of [169Yb]Yb3+ on GAHAnp followed Langmuir-Freundlich isotherm and pseudo-second order kinetics. The mechanism of incorporation of [169Yb]Yb+3 on GAHAnp was investigated using density functional theory (DFT) and experimentally verified by radiotracer investigations and XAFS studies, which suggested replacement of Ca2+ with Yb3+ in GAHAnp matrix. The [169Yb]Yb-GAHAnp formulation demonstrated excellent in vitro radiochemical stability in physiological media and cell toxicity in Raji cells. SPECT/CT imaging and ex vivo biodistribution carried out after intra-tumoral administration of [169Yb]Yb-GAHAnp in tumor bearing mice showed near-complete retention of the formulation in the tumor mass upto 2 weeks. Tumor growth could be significantly arrested after administration of 30 MBq dose of the formulation compared to the control. CONCLUSIONS: These findings demonstrate the potential utility of synthesized [169Yb]Yb-GAHAnp formulation in the treatment of solid tumors through nanobrachytherapy.