Gold Nanostars: A Novel Platform for Developing 211At-Labeled Agents for Targeted Alpha-Particle Therapy

Aim: To develop an innovative 211 At nanoplatform with high radiolabeling efficiency and low in vivo deastatination for future targeted alpha-particle therapy (TAT) to treat cancer. Methods: Star-shaped gold nanoparticles, gold nanostars (GNS), were used as the platform for 211 At radiolabeling. Radiolabeling efficiency under different reaction conditions was tested. Uptake in the thyroid and stomach after systemic administration was used to evaluate the in vivo stability of 211 At-labeled GNS. A subcutaneous U87MG human glioma xenograft murine model was used to preliminarily evaluate the therapeutic efficacy of 211 At-labeled GNS after intratumoral administration. Results: The efficiency of labeling GNS with 211 At was almost 100% using a simple and rapid synthesis process that was completed in only 1 min. In vitro stability test in serum showed that more than 99% of the 211 At activity remained on the GNS after 24 h incubation at 37°C. In vivo biodistribution results showed low uptake in the thyroid (0.44– 0.64%ID) and stomach (0.21– 0.49%ID) between 0.5 and 21 h after intravenous injection, thus indicating excellent in vivo stability of 211 At-labeled GNS. The preliminary therapeutic efficacy study demonstrated that 211 At labeled GNS substantially reduced tumor growth (P < 0.001; two-way ANOVA) after intratumoral administration. Conclusion: The new 211 At radiolabeling strategy based on GNS has the advantages of a simple process, high labeling efficiency, and minimal in vivo dissociation, making it an attractive potential platform for developing TAT agents that warrants further evaluation in future preclinical studies directed to evaluating prospects for clinical translation. Keywords: astatine-211, 211 At, gold nanostars, GNS, cancer therapy, targeted alpha-particle therapy, TAT