Cyclotron Production of rhenium-186 for metabolic radiotherapy, by proton and deuteron cyclotron irradiation

Since its discovery in 1896, radioactivity has been used in various application areas of physics. In particular, it was immediately clear its potential use in life sciences. In particular, it is actually used in metabolic radiotherapy, which uses radionuclides labelled to suitable molecules (i.e. radiopharmaceuticals). This is a practice well established and successful in the fight against cancer and other diseases. Together with the well-known radionuclides used in medicine, the attention is now focused one the ones of next generation. One of these is rhenium-186g, which is currently used in palliative treatment of bone metastases pain due to its chemical and physical characteristics. The combination of these characteristic makes it particularly suitable for radiotherapeutic purposes, although this goal have not been reached yet. In fact, currently it is produced in thermal nuclear reactor on enriched 185Re target which leads to a low specific activity AS (radionuclide mass / mass isotopic carrier). To enhance this important parameter that determines the suitability for the radiotherapeutic use, other different production routes must be investigated. In particular, it was studied the effectiveness of the rhenium cyclotron production through the 186W(p,n)186gRe and 186W(d,2n)186gRe nuclear reactions. The tungsten targets have been irradiated at the Scanditronix MC40 of the JRC of Ispra (VA) and then transported to the LASA laboratory where they have been measured by HPGe gamma spectrometry. For each target a set of excitation function and thin-target yield (tty) data for the 186W(p,n)186gRe, 186W(d,2n)186gRe, natW(p,xn)181,182(m+g),183,184(m+g)Re, natW(d,xn)181,182(m+g),183,184(m+g)Re and 186W(d,p)187W has been calculated. In all these runs, it was used the stacked foil tecnique which consists in a superimposition of thin tungsten foils interspersed by thin aluminium foils which degrade the beam energy and collect the recoil atoms. Meanwhile, some thick targets have been prepared and then irradiated. In such an experimental condition, the beam is completely stopped inside the thick target; in this case is so possible to measure the thick target yield (TTY) of the different radioisotopes. These experimental data were then compared with those obtained by the integration of the curves of the thin target yields. Unlike similar works in literature, in this one an innovative analytical method for the evaluation of the mean energy uncertainty associated to each target has been introduced. Moreover, the problem linked to the self-absorption of low energies gamma rays due to the high Z of tungsten was faced and solved introducing a correction factor. Protons and deuterons irradiations provided interesting conclusions; in particular the ones carried out on enriched 99.9% 186W targets gave some information on the most effective production route from a commercial point of view. This preliminary information was combined to the ones obtained by the radiochemical separation. In fact, an effective radiochemical separation was set out in order to separate rhenium radioisotopes from the tungsten matrix with a subsequent quality control of the obtained solutions. The chemical separation, based on a 'wet' technique, consisted in a plastic mini-column filled in with acid Activated Aluminium Oxide (AAO) with, as mobile phase, HNO3 7 M. With such a technique it was possible to obtain the radiochromatograms of the elution. It is important to notice that, in the cases of enriched tungsten target, there was the side production of radioactive 187W which acted as radio-tracer. In fact, it was possible to verify the possible unwanted co-elution of tungsten (i.e. breakthrough) which represents a radionuclidic impurity. This radiochemical separation provides for the dissolution of the activated tungsten powder target by using a mixture of HNO3/. The process was set out by the addition of small amounts of hyper pure water under continuous warming and stirring in order to facilitate the dissolution itself. Once it was totally dissolved, the solution was warming for an enough period of time so that the azeotropic mixture of HF/H2O was completely evaporated and the azeotropic mixture HNO3/H2O (HNO3 7 M) was reached, which is necessary for the radiochemical separation. From the resulting solution a standard was picked up and the remainder was put on the head of the column. The eluate was collected in several vials that have been measured by using gamma spectrometry inorder to obtain a radiochromatogram. Moreover, exploiting the standard of known mass and volume, the radiochemical yield of the developed method was calculated. From the whole data collected, it was possible to demonstrate how, in the case of deuteron irradiations, the radionuclidic purity, linked to the rhenium radionuclides, was greater than the one obtained by proton irradiations and, besides, how this purity remained high (> 99%) for a longer period of time. Finally, comparing the integrated thin target yields of the two different production routes, it was clear that the yield obtained by deuterons beam is comparable to the one performed by protons beam for energies up to 9 MeV while, for higher energy, the first method is extremely more advantageous. In fact, taking into account that, at the same energy, deuterons have a range in the material lower than the protons, it is possible to conclude that a minor tungsten matrix is required to produce an equivalent amount of rhenium-186, which implies lower costs and easier dissolution processes