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

99mTc 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 99mTc, 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 (t½¼6 h) is ideal for diagnostic nuclear imaging. A patient can be injected with a small amount of 99mTc and within 24 h almost 94% of the injected radionuclide would have decayed and left the body, limiting the patient’s radiation exposure. 99mTc is usually supplied to hospitals through a 99Mo/99mTc radionuclide generator system where it is produced from the b decay of the parent nuclide 99Mo (t½¼66 h), which is produced in nuclear reactors via neutron fission. Recently, the interruption of the global supply chain of reactor-produced 99Mo, has forced the scientific community to investigate alternative production routes for 99mTc. One solution was to consider cyclotron-based methods as potential replacement of reactorbased technology and the nuclear reaction 100Mo(p,2n)99mTc emerged as the most worthwhile approach. This review reports some achievements about 99mTc produced by medical cyclotrons. In particular, the available technologies for target design, the most efficient extraction and separation procedure developed for the purification of 99mTc from the irradiated targets, the preparation of high purity 99mTc radiopharmaceuticals and the first clinical studies carried out with cyclotron produced 99mTc are described.