Recent achievements in Tc-99m radiopharmaceutical direct production by medical cyclotrons

Tc-99m is the most commonly used radionuclide in the field of diagnostic imaging, a noninvasive method intended to diagnose a disease, assess the disease state and monitor the effects of treatments. Annually, the use of Tc-99m, covers about 85% of nuclear medicine applications. This isotope releases gamma rays at about the same wavelength as conventional X-ray diagnostic equipment, and owing to its short half-life (t(1/2) = 6 h) is ideal for diagnostic nuclear imaging. A patient can be injected with a small amount of Tc-99m and within 24 h almost 94% of the injected radionuclide would have decayed and left the body, limiting the patient's radiation exposure. Tc-99m is usually supplied to hospitals through a Mo-99/Tc-99m radionuclide generator system where it is produced from the beta decay of the parent nuclide Mo-99 (t(1/2) = 66 h), which is produced in nuclear reactors via neutron fission. Recently, the interruption of the global supply chain of reactor-produced Mo-99, has forced the scientific community to investigate alternative production routes for Tc-99m. One solution was to consider cyclotron-based methods as potential replacement of reactor-based technology and the nuclear reaction Mo-100(p,2n)Tc-99m emerged as the most worthwhile approach. This review reports some achievements about Tc-99m produced by medical cyclotrons. In particular, the available technologies for target design, the most efficient extraction and separation procedure developed for the purification of Tc-99m from the irradiated targets, the preparation of high purity Tc-99m radiopharmaceuticals and the first clinical studies carried out with cyclotron produced Tc-99m are described.