TRENDS IN RADIOISOTOPES AND RADIOLABELING METHODS

Summary: Radiopharmaceutical research and bioscience or medical applications have changed during the decades in the function of available technologies for radioisotope production and imaging detection technologies. In the 1940s to 1960s year, radioisotopes were supplied by reactor production, such as 131I for thyroid uptake study, 197Hg, 203Hg-chlormerodrin for brain scans, 198Au-colloid for liver scans, and 85Sr-chloride for the bone scans. In the late 1960s, with the development of the gamma camera by Hal Anger, and the 99Mo/99mTc generators by researchers of the Brookhaven National Laboratory, the focus was moved to research and diagnostic application of 99mTc radiopharmaceuticals, and these compounds have been in use until now. In that age, the chemistry of technetium, including the production of different chelators and radiolabeling processes, were developed. Cyclotron-producing radioisotopes for medical application emerged in 1955, and for a long time, it was used to produce gamma-emitting radionuclides such as 67Ga, 111In, and 201Tl. After the development of PET câmera around 1975, positron-emitting radioisotopes started to be produced routinely in cyclotrons, such as 11C, 13N, and 18F, gaining market status for diagnostic applications after Alfred Wolf and colleagues developed the 18F-FDG, around 1978. In the following year, positron-emitting radiometals 68Ga, 64Cu, and 89Zr, began to be produced on a large scale to label molecules with short or long circulation times in the body. The results in the specificity of the diagnostic opened the possibility of using 90Y and 177Lu, both beta-emitting radioisotopes, to label the same molecules for therapeutic purposes; thus, theranostics pair 68Ga or 64Cu/90Y or 177Lu started to be used in nuclear medicine. From the 2010s, true theranostic pairs gain interest, such as 44gSc/47Sc, 64Cu/67Cu, 83Sr/89Sr, 86Y/90Y, 124I/131I, 152Tb/161Tb, and 152Tb/149Tb, stated to be produced and evaluated for clinical applications. All these developments in radioisotope production and imaging systems also boosted the development of molecule radiolabeling processes, mainly through automated systems, to ensure speed, reproducibility, and less exposure to professionals involved in preparing these molecules. Furthermore, several chelating agents have been developed to complex different metals in a simple, effective, and stable way, such as the DOTA, NOTA, HBED molecules, among others. Conclusão: Trends in radioisotopes and radiolabeling methods result from scientific and technological developments in different areas but with congruent purposes. The result is a large number of products that can be chosen by their physical, chemical, biological, or economic characteristics.