RADIUM: FROM DISCOVERY BY MARIE CURIE TO MEDICAL APPLICATIONS

摘要

In 1905, Marie and Pierre Curie were awarded the Nobel Prize, jointly with the physicist Henri Becquerel, for the discovery of natural "radio-activity", a word that Marie Curie introduced herself. In 1934, Irene and Frederic Joliot-Curie discovered the artificial production of radioactivity at the Curie Institute, founded by Marie Curie twenty years earlier. These two major discoveries led to a vast number of medical applications, from external radiation therapy to the use of radioi-sotopes for internal radiotherapy and in vivo or in vitro investigations of physiological processes. For the last two decades, medical uses of radioisotopes have known an exceptional expansion through the development of molecular imaging. This has offered us the opportunity to characterize different in vivo biological processes, such as metabolism, proliferation, hypoxia in oncology and has allowed to improve the patient management. Marie Curie worked hard to characterize two elements, polonium and radium, and determined their spectrum and atomic weight. In advance of his time, Pierre Curie understood the potential role that natural radium-226 could have for medical uses, which led to the first treatment of der-matological diseases and cancers. One century after its discovery, radium-226 in radiation therapy was abandoned for radiation protection reasons. However, for the last decade, medical applications of radium have experienced a renewal with the development of radium-223 as radio-pharmaceutical. Indeed, this radioisotope was successfully developed in the treatment of bone metastases in patients with hormone-refractory prostate cancer. It is produced by neutron capture of radium-226 leading to radium-227, which decays with a 42-min half-life to actinium-227. Then, radium-223, as a radioactive daughter of actinium-227, can be obtained on a relatively easy way by elution of a generator containing actinium-227. Finally, the 11-day half-life of radium-223 allows its preparation and worldwide distribution from the production site based in Norway. Low gamma-irradiation of radium-223 is favourable from the point of view of handling, radiation protection and treatment on an outpatient basis, but radiation protection rules have to be strictly respected during the administration to patients. External-beam radiation has shown its efficacy to palliate painful bone metastases, when disease is not widespread, but no significant improvement in overall survival. Radium-223, a bone-seeking alpha-emitter, is really the first radiopharmaceutical to have shown a significant improvement in overall survival in a large population of prostate cancer patients with bone metastases, compared to other radioisotopes beta-emitters, such as phosphore-32 and strontium-89. The higher efficacy and the lower toxicity observed with radium-223 at therapeutically relevant dosages can be explained by the differences of radiobiological effects. Alpha-emitters are densely ionising particles, with a shorter range in tissues of less than 100 μm and a high linear energy transfer (LET), compared to beta-emitters. They induce non-reparable double DNA-strand breaks More than one century after Marie Curie was awarded the Nobel Prize for the discovery of natural radium and had founded the Curie Institute in Paris, which is nowadays a Cancer Research Centre, we recently assisted in the development of an artificially-produced isotope of natural radium in the treatment of prostate cancer patients with bone metastases.