44Sc production from enriched 47TiO2 targets with a medical cyclotron.

44Sc is a ß+-emitter which has been extensively studied for nuclear medicine applications. Its promising decay characteristics [t1/2 = 3.97 h, E [Formula: see text] = 632 keV (94.3%), Eγ = 1157 keV (99.9%); 1499 keV (0.91%)] make it highly attractive for clinical PET imaging, offering an alternative to the widely used 68Ga [t1/2 = 67.7 min, E [Formula: see text] = 836 keV (87.7%)]. Notably, its nearly fourfold longer half-life opens avenues for applications with biomolecules having extended biological half-lives and enables the centralized distribution of 44Sc radiopharmaceuticals. An additional advantage of employing 44Sc as a diagnostic radioisotope lies in its counterpart, the ß--emitter 47Sc, which is currently under investigation for targeted radiotherapy. Together, they form an ideal theranostic pair, providing a comprehensive solution for both diagnostic imaging and therapeutic applications in nuclear medicine. At the Bern medical cyclotron, a study to optimize the production of scandium radioisotopes is currently ongoing. In this context, proton irradiation of titanium targets has been investigated, exploiting the reactions 47Ti(p,α)44Sc and 50Ti(p,α)47Sc. This approach enables the production of Sc radioisotopes within a single PET medical cyclotron facility, employing identical chemical procedures for target preparation and post-irradiation processing. In this paper, we report on cross-section measurements of the 47Ti(p,α)44Sc nuclear reaction using 95.7% enriched 47TiO2 targets. On the basis of the obtained results, the production yield and purity were calculated to assess the optimal irradiation conditions. Production tests were performed to confirm these findings.

Cross-section measurement of thulium radioisotopes with an 18 MeV medical PET cyclotron for an optimized 165Er production.

165Er is a pure Auger-electron emitter with promising characteristics for therapeutic applications in nuclear medicine. The short penetration path and high Linear Energy Transfer (LET) of the emitted Auger electrons make 165Er particularly suitable for treating small tumor metastases. Several production methods based on the irradiation with charged particles of Er and Ho targets can be found in the literature. In this paper, we report on the study of 165Er indirect production performed via the 166Er(p,2n)165Tm →165Er reaction at the 18 MeV Bern medical cyclotron. Despite the use of highly enriched 166Er2O3 targets, several Tm radioisotopes are produced during the irradiation, making the knowledge of the cross sections involved crucial. For this reason, a precise investigation of the cross sections of the relevant nuclear reactions in the energy range of interest was performed by irradiating Er2O3 targets with different isotopic enrichment levels and using a method based on the inversion of a linear system of equations. For the reactions 164Er(p, γ)165Tm, 166Er(p,n)166Tm, 166Er(p, γ)167Tm, 167Er(p,3n)165Tm, 167Er(p, γ)168Tm, 168Er(p,2n)167Tm and 170Er(p,3n)168Tm, the nuclear cross section was measured for the first time. From the results obtained, the production yield and purity of the parent radioisotope 165Tm were calculated to assess the optimal irradiation conditions. Several production tests with solid targets were performed to confirm these findings.

Experimental assessment of nuclear cross sections for the production of Tb radioisotopes with a medical cyclotron.

155Tb is one of the most interesting radionuclides for theranostic applications. It is suitable for SPECT imaging and it can be used as a true diagnostic partner of the therapeutic 149Tb and 161Tb. Its production by proton irradiation using enriched 155Gd and 156Gd oxide targets is currently being investigated and represents a promising solution. To achieve the level of radionuclidic purity required in the clinical setting, the co-production of Tb impurities has to be minimized. For this purpose, an accurate knowledge of the cross sections of the nuclear reactions involved is of paramount importance. In this paper, we report on the assessment of cross sections of the reactions 154Gd(p,xn)153,154,154m1,154m2Tb, 155Gd(p,xn)154,154m1,154m2,155Tb, 156Gd(p,xn)155,156Tb and 157Gd(p,2n)156Tb derived with a specific data analysis procedure developed by our group. This method allows to disentangle the nuclear contributions from the production cross section by inverting linear systems of equations and it requires the measurement of the cross sections from as many materials as the reactions involved in the production of the radionuclide under study. For this purpose, the experimental data previously measured by our group at the Bern medical cyclotron by irradiating natural Gd2O3, enriched 155Gd2O3 and enriched 156Gd2O3 targets were used. For some of these nuclear reactions, cross sections were assessed for the first time. On the basis of our findings, production yield and purity can be calculated for any kind of isotopic composition of the enriched material.

Optimized production of 67Cu based on cross section measurements of 67Cu and 64Cu using an 18 MeV medical cyclotron.

RadioNuclide Therapy (RNT) in nuclear medicine is a cancer treatment based on the administration of radioactive substances that specifically target cancer cells in the patient. These radiopharmaceuticals consist of tumor-targeting vectors labeled with ß-, α, or Auger electron-emitting radionuclides. In this framework, 67Cu is receiving increasing interest as it provides ß--particles accompanied by low-energy γ radiation. The latter allows to perform Single Photon Emission Tomography (SPECT) imaging for detecting the radiotracer distribution for an optimized treatment plan and follow-up. Furthermore, 67Cu could be used as therapeutic partner of the ß+-emitters 61Cu and 64Cu, both currently under study for Positron Emission Tomography (PET) imaging, paving the way to the concept of theranostics. The major barrier to a wider use of 67Cu-based radiopharmaceutical is its lack of availability in quantities and qualities suitable for clinical applications. A possible but challenging solution is the proton irradiation of enriched 70Zn targets, using medical cyclotrons equipped with a solid target station. This route was investigated at the Bern medical cyclotron, where an 18 MeV cyclotron is in operation together with a solid target station and a 6-m-long beam transfer line. The cross section of the involved nuclear reactions were accurately measured to optimize the production yield and the radionuclidic purity. Several production tests were performed to confirm the obtained results.

Alternative routes for 64Cu production using an 18 MeV medical cyclotron in view of theranostic applications.

Radiometals play a fundamental role in the development of personalized nuclear medicine. In particular, copper radioisotopes are attracting increasing interest since they offer a varying range of decay modes and half-lives and can be used for imaging (60Cu, 61Cu, 62Cu and 64Cu) and targeted radionuclide therapy (64Cu and 67Cu), providing two of the most promising true theranostic pairs, namely 61Cu/67Cu and 64Cu/67Cu. Currently, the most widely used in clinical applications is 64Cu, which has a unique decay scheme featuring ß+-, ß--decay and electron capture. These characteristics allow its exploitation in both diagnostic and therapeutic fields. However, although 64Cu has extensively been investigated in academic research and preclinical settings, it is still scarcely used in routine clinical practice due to its insufficient availability at an affordable price. In fact, the most commonly used production method involves proton irradiation of enriched 64Ni, which has a very low isotopic abundance and is therefore extremely expensive. In this paper, we report on the study of two alternative production routes, namely the 65Cu(p,pn)64Cu and 67Zn(p, α)64Cu reactions, which enable low and high 64Cu specific activities, respectively. To optimize the 64Cu production, while minimizing the mass of copper used as a target in the first case, or the co-production of other copper radioisotopes in the second case, an accurate knowledge of the production cross sections is of paramount importance. For this reason, the involved nuclear reaction cross sections were measured at the Bern medical cyclotron laboratory by irradiating enriched 65CuO and enriched 67ZnO targets. On the basis of the obtained results, the production yield and purity were calculated to assess the optimal irradiation conditions. Several production tests were performed to confirm these findings.

A novel experimental approach to characterize neutron fields at high- and low-energy particle accelerators.

The characterization of particle accelerator induced neutron fields is challenging but fundamental for research and industrial activities, including radiation protection, neutron metrology, developments of neutron detectors for nuclear and high-energy physics, decommissioning of nuclear facilities, and studies of neutron damage on materials and electronic components. This work reports on the study of a novel approach to the experimental characterization of neutron spectra at two complex accelerator environments, namely the CERF, a high-energy mixed reference field at CERN in Geneva, and the Bern medical cyclotron laboratory, a facility used for multi-disciplinary research activities, and for commercial radioisotope production for nuclear medicine. Measurements were performed through an innovative active neutron spectrometer called DIAMON, a device developed to provide in real time neutron energy spectra without the need of guess distributions. The intercomparison of DIAMON measurements with reference data, Monte Carlo simulations, and with the well-established neutron monitor Berthold LB 6411, has been found to be highly satisfactory in all conditions. It was demonstrated that DIAMON is an almost unique device able to characterize neutron fields induced by hadrons at 120 GeV/c as well as by protons at 18 MeV colliding with different materials. The accurate measurement of neutron spectra at medical cyclotrons during routine radionuclide production for nuclear medicine applications is of paramount importance for the facility decommissioning. The findings of this work are the basis for establishing a methodology for producing controlled proton-induced neutron beams with medical cyclotrons.

47Sc and 46Sc cross-section measurement for an optimized 47Sc production with an 18 MeV medical PET cyclotron.

The availability of novel radionuclides plays a fundamental role in the development of personalized nuclear medicine. In particular, there is growing interest in pairs formed by two radioisotopes of the same element, the so-called true theranostic pairs, such as 61,64Cu/67Cu, 43,44Sc/47Sc and 155Tb/149,161Tb. In this case, the two radionuclides have identical kinetics and chemical reactivity, allowing to predict whether the patient will benefit from a therapeutic treatment on the basis of nuclear imaging data. 47Sc [t1/2 = 3.349 d, E [Formula: see text] = 440.9 keV (68.4%); 600.3 keV (31.6%), Eγ = 159.4 keV (68.3%)] is a promising radionuclide for theranostic applications in nuclear medicine. Its physical characteristics make it suitable for radionuclide therapy and allow SPECT imaging during treatment. Moreover, 47Sc is foreseen as the therapeutic partner of the ß+-emitters 43Sc and 44Sc, both under study for PET imaging, opening new avenues towards the true theranostics concept. 47Sc can be produced by proton irradiation of an enriched 50Ti oxide target with a medical cyclotron equipped with a solid target station. To optimize the production yield and the radionuclidic purity, an accurate knowledge of the production cross sections is necessary. In this paper, we report on measurements of the production cross section of 47Sc and 46Sc using enriched 50Ti titanium oxide targets, performed at the Bern University Hospital cyclotron laboratory. On the basis of the obtained results, a study of the production yield and purity was performed to assess the optimal irradiation conditions. A production test was also carried out to confirm these findings.

Cross-section measurement for an optimized 61Cu production at an 18 MeV medical cyclotron from natural Zn and enriched 64Zn solid targets.

The availability of novel medical radionuclides is a key point in the development of personalised nuclear medicine. In particular, copper radioisotopes are attracting considerable interest as they can be used to label various molecules of medical interest, such as proteins and peptides, and offer two of the most promising true theranostic pairs, namely 61Cu/67Cu and 64Cu/67Cu. Although 64Cu (t1/2 = 12.7006 h, ß+: 17.6%, ß-: 38.5%) is nowadays the most commonly used as a diagnostic radionuclide, 61Cu (t1/2 = 3.339 h, ß+: 61%) features more favourable nuclear properties, such as a higher positron decay fraction and the absence of ß- emissions. To date, the production of 61Cu has been carried out irradiating highly enriched 61Ni targets with a low energy proton beam. However, the use of the very expensive 61Ni targets requires an efficient recovery of the target material and makes this method quite inconvenient. Another promising production route is the proton irradiation of natural Zn or enriched 64Zn targets, exploiting the (p,α) nuclear reaction. Along this line, a research program is ongoing at the Bern medical cyclotron, equipped with an external beam transfer line and a solid target station. In this paper, we report on cross-section measurements of the 64Zn(p,α)61Cu nuclear reaction using natural Zn and enriched 64Zn material, which served as the basis to perform optimized 61Cu production tests with solid targets.

Cross section measurement of terbium radioisotopes for an optimized 155Tb production with an 18 MeV medical PET cyclotron.

155Tb [t1/2 = 5.32 d, Eγ = 87 keV (32%); 105 keV (25%) (IAEA, 2021)] is a novel promising radionuclide for theranostic applications in nuclear medicine. Its physical properties make it suitable for single photon emission computed tomography (SPECT) imaging, while its chemistry allows it to be used as a diagnostic partner for therapeutic radiolanthanides or pseudo-radiolanthanides, such as 177Lu and 90Y. Moreover, 155Tb could be used as a precise diagnostic match for the ß--emitter 161Tb, opening doors for the true theranostics concept. The availability of 155Tb in quantity and quality suitable for medical applications is an open issue and its production with medical cyclotrons via the 155Gd(p,n)155Tb and 156Gd(p,2n)155Tb nuclear reactions represents a possible but challenging solution. For this purpose, an accurate knowledge of the production cross sections is mandatory. In this paper, we report on the measurement of the production cross sections of 155Tb and other terbium radionuclides formed by proton irradiation of natGd2O3, 155Gd2O3 and 156Gd2O3 enriched targets, performed at the Bern University Hospital cyclotron laboratory. On the basis of the obtained results, the production yield and purity were calculated to assess the optimal irradiation conditions. The results of several production tests are also presented.