Abstract
To facilitate multicentre clinical studies on targeted alpha therapy, it is necessary to develop an automated, on-site procedure for conjugating rare, short-lived, alpha-emitting radionuclides to biomolecules. Astatine-211 is one of the few alpha-emitting nuclides with appropriate chemical and physical properties for use in targeted therapies for cancer. Due to the very short range of the emitted α-particles, this therapy is particularly suited to treating occult, disseminated cancers. Astatine is not intrinsically tumour-specific; therefore, it requires an appropriate tumour-specific targeting vector, which can guide the radiation to the cancer cells. Consequently, an appropriate method is required for coupling the nuclide to the vector. To increase the availability of astatine-211 radiopharmaceuticals for targeted alpha therapy, their production should be automated. Here, we present a method that combines dry distillation of astatine-211 and a synthesis module for producing radiopharmaceuticals into a process platform. This platform will standardize production of astatinated radiopharmaceuticals, and hence, it will facilitate large clinical studies focused on this promising, but chemically challenging, alpha-emitting radionuclide. In this work, we describe the process platform, and we demonstrate the production of both astaine-211, for preclinical use, and astatine-211 labelled antibodies.
Highlights
To facilitate multicentre clinical studies on targeted alpha therapy, it is necessary to develop an automated, on-site procedure for conjugating rare, short-lived, alpha-emitting radionuclides to biomolecules
The automated platform (Fig. 2) comprises a tube furnace with quartz glassware for distillation, which is connected in tandem to a radiopharmaceutical synthesis module
The system was adapted to fit inside a glovebox or a small lead-shielded, hot-cell to minimize exposure to the volatile, radioactive astatine
Summary
To facilitate multicentre clinical studies on targeted alpha therapy, it is necessary to develop an automated, on-site procedure for conjugating rare, short-lived, alpha-emitting radionuclides to biomolecules. We present a method that combines dry distillation of astatine-211 and a synthesis module for producing radiopharmaceuticals into a process platform This platform will standardize production of astatinated radiopharmaceuticals, and it will facilitate large clinical studies focused on this promising, but chemically challenging, alpha-emitting radionuclide. Targeted alpha therapy takes advantage of the short tissue range (50–100 μ m) of alpha particles When these nuclides are targeted to malignant cells, they deliver a high local, extremely cytotoxic, radiation dose to the tumour, while surrounding healthy tissue is spared. This feature facilitates the treatment of disseminated cancers, such as micro tumours or single malignant cells. At-211 must be converted to a www.nature.com/scientificreports/
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