Properties and applications of astatine in nuclear medicine

Discovered in 1896 by Henry Becquerel, the phenomenon of radioactivity and its associated ionizing radiation was rapidly exploited for therapeutic purposes with the development of brachytherapy. When a radioactive isotope or radioisotope decays, it generates a particle and/or high-energy electromagnetic radiation that can cause irreparable damage to surrounding tumour cells, leading to their death. Since the early days of nuclear medicine, when the radioactive source was implanted directly into the tumor using a needle, the discipline has evolved towards a more refined use known as vectorized radiotherapy, in which the radioisotope is attached to a vector specific to the type of tumor to be targeted, before being injected into the patient. With this approach, even deep-seated and microscopic tumors can in principle be treated while sparing the surrounding healthy tissue. Depending on the type of tumour to be treated, the choice of radioisotope and vector must be perfectly matched.

Alpha particles emitted during radioactive decay are the most energetic and lethal to cells, but they penetrate biological tissues by only a few tens of micrometers. For this reason, α-particle emitters are effective in the treatment of microtumors encountered in residual disease after conventional treatment, or when the disease evolves into a cancer with micrometastases, as well as in the case of hematological cancers expressed by the production of isolated circulating tumor cells. As irradiation is extremely localized, surrounding healthy cells are spared. A limited number of alpha particle emitters of interest to nuclear medicine have been identified. Among them, astatine-211 has some of the most interesting physical characteristics for this type of application: a half-life of 7.2 h, which is adapted to the biological half-life of a large number of vectors, and two decay branches each leading to the emission of an α particle. In addition, appropriate chemical methods are needed to create the radionuclide-vector pair that will form the radiopharmaceutical to be administered to the patient. However, despite the discovery of astatine in the 1930s, its chemistry remains difficult to understand, the main reason being the absence of stable isotopes, which complicates the study of this element's properties.

A better understanding of this element, which will enable us to optimize the design of vectors radiolabeled with astatine-211, is therefore a major challenge for the development of vectorized radiotherapy for cancer.

In this context, this article discusses :

• the phenomenon of radioactivity and the properties of ionizing radiation in cancer treatment;

• the chemical element astatine and...