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

Area of Science:

• Nanotechnology
• Radiochemistry
• Oncology

Background:

• Targeted alpha-particle therapy (TAT) offers a promising approach for cancer treatment due to the high cytotoxicity of alpha emitters.
• Developing stable radiolabeled nanoplatforms is crucial for effective TAT delivery and minimizing off-target effects.

Purpose of the Study:

• To create an innovative ²¹¹At nanoplatform with high radiolabeling efficiency and reduced in vivo de-radonization.
• To assess the potential of this platform for future targeted alpha-particle therapy (TAT) in cancer treatment.

Main Methods:

• Gold nanostars (GNS) were utilized as the nanoplatform for ²¹¹At radiolabeling.
• Radiolabeling efficiency was optimized under various conditions.
• In vivo stability was evaluated by measuring thyroid and stomach uptake post-administration.
• Preliminary therapeutic efficacy was assessed in a U87MG human glioma xenograft murine model.

Main Results:

• Near 100% radiolabeling efficiency of GNS with ²¹¹At was achieved rapidly (1 minute).
• In vitro stability in serum exceeded 99% ²¹¹At retention on GNS after 24 hours.
• In vivo studies showed minimal thyroid and stomach uptake, indicating excellent stability.
• Intratumoral administration of ²¹¹At-labeled GNS significantly reduced tumor growth in a murine model.

Conclusions:

• The ²¹¹At radiolabeling strategy using GNS is simple, efficient, and exhibits minimal in vivo dissociation.
• This GNS-based platform is a promising candidate for developing TAT agents.
• Further preclinical evaluation is warranted for potential clinical translation.