Radioisotopes for Therapy and Development of Therapeutic Radiopharmaceuticals

In recent years there has been a rapid expansion in the use of radionuclides for therapeutic purposes. The potential usefulness of a particular radioisotope depends on many factors: physical data (half-life, energy of beta-particles, gamma ray emissions), production method including separation, labeling and targeting properties of a radionuclide carrier molecule. Depending on the production mode, the radioisotope can be obtained in the pure form (without any carrier) or in the form of the mixture of isotopes, containing also the stable forms. The specific activity is than defined as radioactivity of a certain radioisotope in this mixture. Several beta-emitting radionuclides for targeted radionuclide therapy can be produced in the nuclear reactors, including generator systems, and the list of other potentially useful isotopes is not yet closed. Among the radionuclides used for cancer therapy, 131I, 90Y, 188Re, 166Ho and 153Sm have found applications in a number of clinical procedures and have been used for cancer therapy, bone pain palliation, radiosynovectomy, intravascular radiation therapy and other disorders. Extensive research in the field of radiopharmaceuticals and nuclear medicine practices have lead to the identification of other radionuclides including 177Lu, 161Tb, 67Cu, 47Sc with promising radionuclide physical and chemical properties, which still need to be explored. The latter two are of interest due to their positron emitting 'twins' i.e. 64Cu and 44Sc, which can be used for diagnostic imaging and therapy follow up using the same carrier molecules. On the other hand various techniques have been developed in order to improve the therapeutic effect such as the isotope cocktail approach, loco-regional administration, pre-targeting or combination with chemotherapy, providing new therapy options. The most popular in last years were carrier-free 90Y and 177Lu as well as carrier-added 177Lu used for labeling of peptides specific to somatostatin receptors. Extensive experiences of several groups, also supported by the IAEA programs, indicated that the specific activity, chemical and radionuclidic purity need special consideration. Most of bifunctional chelating systems used as chelators for 90Y and 177Lu form competitive complexes with cations of copper, iron, nickel, zinc, lead etc. Therefore presence of these elements as impurities in the solvents used in the production process or in the final product influences negatively the labelling yield. The same relates to the excess of cold element in the low specific activity preparations and the excess of peptide needed to bind the required radioactivity of isotope. The variation in peptide amount and specific activity of the radiolabelled peptide effects the tissue distribution in both rats and humans, thus indicating that the sensitivity of the detection of tumours by receptor scintigraphy and the success of radionuclide therapy will vary with the mass of the radiolabelled injected. All these considerations need to be in focus when designing the new radiopharmaceutical in order to assure its efficient use in clinical trials. (author)