Chemical methods for the production of astatine-211 labeled radiophrmaceuticals
Alpha particles can focus large amount of energy over a few cell diameters allowing for targeted tumor cell elimination with minimal damage to surrounding healthy tissues. These properties make α-emitters significantly more effective and safe for killing tumor cells than either conventional external beam therapy or commercially available beta particle emitters. Therefore, α-particles are optimal candidates for molecularly targeted radiotherapy: α-particle labeled biomolecules can be developed to allow tumor cell specific uptake. Cancerous cells can be effectively eliminated with minimized healthy tissues damage. As a result, targeting α-emitters to cancer cells has emerged as a particularly promising approach for treating strategically sensitive tumor sites such as those in the central nervous system. Among all the α-particles, 211Astatine (211Ast) has been considered the most promising one for cancer therapy. However, 211Ast’s potential has never been realized and its use has not been widespread. The biggest challenge is that 211Ast decays quickly into a radio-inactive form that cannot be used for cancer therapy. This instability makes it hard to produce 211Ast-labeled compounds and limits the shipping of labeled compound from production site to remote clinics.
To fulfill α-emitters’ potential in cancer therapy, Zalutsky lab has discovered methods to stabilize 211Ast in a manner that allows the preparation of 211Ast-labeled compounds in high yields and high levels of radioactivity. Specifically, 211Ast can be stabilized during the shipping process with solutions containing oxidant. Once 211Ast arrives on clinical sites, inventors provided a convenient and high efficiency method to label compounds with 211Ast. With this invention, the limitations in applying 211Ast for cancer therapy can be overcome. In addition, two clinical trials with 211Ast targeted radiotherapy have been conducted at Duke Medical Center and both have demonstrated feasible, safe, and promising antitumor benefits.
- The invention can be readily developed into a 211Ast labeling kit with cheap reagents
- 211Ast has high reliability in targeted cancer cell killing results both in cell lines and animal models
- Early clinical trials demonstrated feasibility, safety, and promising antitumor benefits for patients