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 (t_½ = 6 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 β decay of the parent nuclide ⁹⁹Mo (t_½ = 66 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 reactor-based 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.