Role of Microwave radiation on Radiopharmaceutical Preparations

The activating effects of Microwaves on organic reactions were repeatedly demonstrated since the early reports in 1986. The majority of these interesting results were ascribed to the MW thermal effect. Nevertheless, the debate on the involvement of the so-called ”non thermal” effects is still opened, since the solely heating effect cannot explain the experimental results. We introduced the use of MW to exploit the positive effects of these radiations in radiopharmaceuticals, or radio labelled molecules, synthesis, performing at the same time theoretical studies to define which MW effects were actually involved. The increase of the reaction rate is of fundamental importance in radiochemistry especially in the case of the short-life isotopes used in radio diagnosis. At first we studied the performances of 99mTc-MAG3 complex synthesis under MW irradiation. 99mTc is the most widely used nuclide to produce diagnostic radiopharmaceuticals, the mercaptoacetyltriglycine (MAG3) is a compound that, labelled by 99mTc through the formation of a chelation complex, is very useful in kidney diagnostic scintigraphy. The microwave treatment increased the hydrolysis rate of MAG3 reducing the time for a complete labelling: 3 min of MW treatment instead of the 10 min of boiling water bath. Moreover, the complete labelling under microwave treatment was reached at a temperature about 20°C lower than in the traditional procedure. Both these differences are surely decisive in reducing the probability of MAG3-SH degradation and the consequent formation of unwanted labelled by-products. The labelling of rifamicine, was requested to study its pharmacokinetics in vivo after oral administration, in particular its absorbtion at the intestinal level. This antibiotic has a molecular structure forming a loop, theoretically able to complex ions. For this reason the chosen radionuclide was again 99mTc. A reduced form, rifamicine SV was also used. The attempt to label rifamicine with freshly prepared 99mTc under traditional conditions failed. When the experiment was repeated employing “older” 99mTc, i.e. prepared 24-48 h before use, better results were obtained. Under MW irradiation the labelling yield resulted very good using both fresh and old 99mTc. The effectiveness of MW in producing rifamicine-99mTc complex independently from the Tc age is ascribed to the formation, during MW heating, of “hot spots”, which mimic the effects of “hot atoms” probably present in old 99mTc preparations. Finally, we decided to make theoretical kinetics studies of the influence of MW on some well known, simple pseudo-first order, hydrolysis reactions: that one of indomethacin and of the NO2 group of various nitroimidazoles. The Arrhenius activation energy values of the reactions performed both under MW and conventional heating were calculated and compared. No changes occurred in the reaction mechanism under microwave, both for nitroimidazoles and indometacine, but the reaction rate is increased under irradiation. In the case of Indometacine the hydrolysis rate can be even 50 time higher than using traditional heating.