Production of 203Pb from enriched 205Tl using deuteron beams.

Lead-203 is a SPECT emitter that can be used in theranostic applications as an imaging counterpart of lead-212 which is intended to be used for alpha therapy as lead-212/bismuth-212 in-vivo generator. In our study, we explore the production of lead-203 using enriched thallium-205 target irradiated by a deuteron beam. Excitation functions of deuteron induced reactions leading to the formation of 204m,203m2+m1+g,202m,201m+gPb, 202Tl and 203m+gHg isotopes were determined experimentally in the energy range from 21 MeV to 34 MeV. Cross sections were measured using the stacked foils technique and a set of two monitor foils, natNi and natTi for beam intensity evaluation. The experimental excitation functions of the investigated reactions were compared with the published data and also with the TENDL-2021 nuclear database. From our experimental data, we calculated lead-203 thick target yield in the energy range between 30 MeV and 32.5 MeV to be 56.7 MBq/µAh ±6.1 MBq/µAh. This value is compatible with large batch production showing that deuteron beams can be used for a routine production process. However, special attention must be paid to 203Hg and other lead contaminants.

Study of terbium production from enriched Gd targets via the reaction 155Gd(d,2n)155Tb.

The terbium (Tb) family has attracted much attention in recent years thanks to the diagnostic and therapeutic applications of the quadruplet 149Tb, 152Tb, 155Tb and 161Tb. However, the scarce availability of Tb radioisotopes is one of the main reasons hindering its clinical applications. To increase its availability, this work proposes to use enriched gadolinium (Gd) targets to produce some Tb radioisotopes (149Tb, 152Tb, and 155Tb) via deuteron-induced reactions in cyclotrons. The production of the Auger and gamma emitter 155Tb was chosen as a case study because the 155Gd enrichment (92.8%) is the highest available from all Gd stable isotopes. The involved reaction is 155Gd(d,2n)155Tb. Using enriched thin Gd-containing targets, cross-sections of the reactions 155Gd(d,x)153,154,155,156Tb have been measured at the GIP ARRONAX cyclotron facility with a beam energy ranging from 8 MeV to 30 MeV. This measurement allows for estimating the production yield and the purity of 155Tb, and for determining the irradiation parameters for large production batches. A thick enriched 155Gd2O3 target has been then irradiated with an incident energy of 15.1 MeV and a beam current of 368 nA for 1 h. The production yield of 155Tb is 10.2 MBq/µA/h at End Of Bombardment (EOB) and the purity is 89% after 14 days of decay. These experimental values are consistent with estimation based on measured cross-sections. A comparison of the deuteron-induced and proton-induced production routes is also presented in this paper.

Can we reach suitable 161Tb purity for medical applications using the 160Gd(d,n) reaction?

Terbium is a chemical element that has several radioactive isotopes with suitable physical characteristics to be used in medical applications either for imaging or for therapy. This makes terbium a promising element to implement the theranostic approach. For therapeutic applications, 161Tb (T1/2 = 6.89 d) is suitable for targeted ß-therapy. The main production route is through neutron capture reaction in nuclear reactors. In this work, we explored an alternative production route, the 160Gd(d,n)161Tb reaction. We have measured its production cross-section as well as those of possible co-produced contaminants, with a special focus on 160Tb (T1/2 = 72.3 d). To achieve this, cross-section measurements were made from natural gadolinium target. Production yields of 10.3 MBq/µA/h for the 161Tb and 1.5 MBq/µA/h for the 160Tb were obtained at 20 MeV. A161Tb radionuclidic purity of 86% was achieved over the 8 MeV-20 MeV energy range. The co-production of other terbium isotopes limits the interest of using higher energies. Based on the limited purity of 161Tb using the 160Gd(d,n)161Tb reaction, we conclude that it is not a production route suitable for medical applications. Although, this may be reconsidered when mass separation technique with high efficiency will be available.

Electrochemical co-deposition of Ni-Gd2O3 for composite thin targets preparation: Production of 155Tb as a case study.

In the last years, 155Tb has attracted enormous interest due to its potential role in theranostics in nuclear medicine. To estimate its production yield, the aim of this study was to develop a method to prepare thin Gd-enriched-containing targets aimed at the 155Gd(d, 2n)155Tb nuclear cross section measurement. To this end, the electrochemical co-deposition method has been chosen to manufacture Ni-Gd2O3 composite targets. Several process parameters that have an impact on the deposit quality, have been investigated to increase the incorporation of Gd mass (up to 3 mg). To validate the concept, seven targets made by natural Gd were irradiated with deuteron beams at the GIP ARRONAX facility cyclotron, with an energy range ranging from 8 MeV to 30 MeV to extract the cross section values by using the stacked-foils method. Results obtained turned out to have great consistency with existing published data thus validating the proposed method. Therefore, an alternative target manufacturing concept aimed at cross section measurement is presented in this work.

Technical note: Proton beam dosimetry at ultra-high dose rates (FLASH): Evaluation of GAFchromic™ (EBT3, EBT-XD) and OrthoChromic (OC-1) film performances.

PURPOSE: The ARRONAX cyclotron facility offers the possibility to deliver proton beams from low to ultra-high dose rates (UHDR). As a good control of the dosimetry is a prerequisite of UHDR experimentations, we evaluated in different conditions the usability and the dose rate dependency of several radiochromic films commonly used for dosimetry in radiotherapy. METHODS: We compared the dose rate dependency of three types of radiochromic films: GAFchromic™ EBT3 and GAFchromic™ EBT-XD (Ashland Inc., Wayne, NJ, USA), and OrthoChromic OC-1 (OrthoChrome Inc., Hillsborough, NJ, USA), after proton irradiations at various mean dose rates (0.25, 40, 1500, and 7500 Gy/s) and for 10 doses (2-130 Gy). We also evaluated the dose rate dependency of each film considering beam structures, from single pulse to multiple pulses with various frequencies. RESULTS: EBT3 and EBT-XD films showed differences of response between conventional (0.25 Gy/s) and UHDR (7500 Gy/s) conditions, above 10 Gy. On the contrary, OC-1 films did not present overall difference of response for doses except below 3 Gy. We observed an increase of the netOD with the mean dose rate for EBT3 and EBT-XD films. OC-1 films did not show any impact of the mean dose rate up to 7500 Gy/s, above 3 Gy. No difference was found based on the beam structure, for all three types of films. CONCLUSIONS: EBT3 and EBT-XD radiochromic films should be used with caution for the dosimetry of UHDR proton beams over 10 Gy. Their overresponse, which increases with mean dose rate and dose, could lead to non-negligible overestimations of the absolute dose. OC-1 films are dose rate independent up to 7500 Gy/s in proton beams. Films response is not impacted by the beam structure. A broader investigation of the usability of OC-1 films in UHDR conditions should be conducted at intermediate and higher mean dose rates and other beam energies.

Is 70Zn(d,x)67Cu the Best Way to Produce 67Cu for Medical Applications?

The pair of copper radionuclides 64Cu/67Cu (T1/2 = 12. 7 h/61.8 h) allows, respectively, PET imaging and targeted beta therapy. An analysis of the different production routes of 67Cu with charged particles was performed and the reaction 70Zn(d,x) route was identified as a promising one. It may allow the production of 67Cu without 64Cu. The production cross section has been measured up to 28.7 MeV. Measurements were done using the well-known stacked-foils technique using 97.5% enriched 70Zn homemade electroplated targets. These measurements complement at higher incident energies the only set of data available in nuclear databases. The results show that using a 26 MeV deuteron beam and a highly enriched 70Zn target, it is possible to produce high purity 67Cu comparable to that obtained using photoproduction. This production route can be of interest for future linear accelerators under development where mA deuteron beams can be available if adequate targetry is developed.

A Monte Carlo Determination of Dose and Range Uncertainties for Preclinical Studies with a Proton Beam.

Proton therapy (PRT) is an irradiation technique that aims at limiting normal tissue damage while maintaining the tumor response. To study its specificities, the ARRONAX cyclotron is currently developing a preclinical structure compatible with biological experiments. A prerequisite is to identify and control uncertainties on the ARRONAX beamline, which can lead to significant biases in the observed biological results and dose-response relationships, as for any facility. This paper summarizes and quantifies the impact of uncertainty on proton range, absorbed dose, and dose homogeneity in a preclinical context of cell or small animal irradiation on the Bragg curve, using Monte Carlo simulations. All possible sources of uncertainty were investigated and discussed independently. Those with a significant impact were identified, and protocols were established to reduce their consequences. Overall, the uncertainties evaluated were similar to those from clinical practice and are considered compatible with the performance of radiobiological experiments, as well as the study of dose-response relationships on this proton beam. Another conclusion of this study is that Monte Carlo simulations can be used to help build preclinical lines in other setups.

THE RADIOBIOLOGICAL PLATFORM AT ARRONAX.

The cyclotron ARRONAX can deliver different types of particles (protons, deuterons, alpha-particles) in an energy range up to 68 MeV. One of its six experimental halls is dedicated to studying the interactions of radiation with matter including living matter. A horizontal beamline for cell irradiation has been setup and characterized. The radiobiological characterization was done in terms of V79 cells survival after irradiation with 68 MeV protons. The results demonstrate that radiobiological studies can be successfully performed confirming the high potential of the facility.

Production of Sc medical radioisotopes with proton and deuteron beams.

Proton and deuteron beams (15.3 and 6.8 MeV, respectively) extracted from the PETtrace medical cyclotron at the Radiopharmaceuticals Production and Research Centre in the University of Warsaw, Heavy Ion Laboratory, 28 MeV protons from the C30 cyclotron at the National Centre for Nuclear Research, Swierk, near Warsaw and 33 MeV protons from the ARRONAX accelerator, Nantes were used to produce and investigate the medically interesting Sc radioisotopes. Both natural and isotopically enriched CaCO3 and TiO2 targets were used (42Ca, 43Ca, 44Ca, 48Ca, 48Ti). The production efficiency and isotopic purity were determined and are reported here for the highest commercially available enrichments of the target material. The Thick Target Yield, Activities at the End of Bombardment (EOB) and the relative activities of produced impurities at EOB are reported for 43Sc, 44gSc, 44mSc and 47Sc produced with particle energies below 33 MeV.

Is there an interest to use deuteron beams to produce non-conventional radionuclides?

With the recent interest on the theranostic approach, there has been a renewed interest for alternative radionuclides in nuclear medicine. They can be produced using common production routes, i.e., using protons accelerated by biomedical cyclotrons or neutrons produced in research reactors. However, in some cases, it can be more valuable to use deuterons as projectiles. In the case of Cu-64, smaller quantities of the expensive target material, Ni-64, are used with deuterons as compared with protons for the same produced activity. For the Sc-44m/Sc-44g generator, deuterons afford a higher Sc-44m production yield than with protons. Finally, in the case of Re-186g, deuterons lead to a production yield five times higher than protons. These three examples show that it is of interest to consider not only protons or neutrons but also deuterons to produce alternative radionuclides.

Measurements of (186)Re production cross section induced by deuterons on (nat)W target at ARRONAX facility.

INTRODUCTION: The ARRONAX cyclotron, acronym for "Accelerator for Research in Radiochemistry and Oncology at Nantes Atlantique" is a new facility installed in Nantes, France. A dedicated program has been launched on production of innovative radioisotopes for PET imaging and for ß- and α targeted radiotherapy using protons or α particles. Since the accelerator is also able to deliver deuteron beams up to 35 MeV, we have reconsidered the possibility of using them to produce medical isotopes. Indeed, in some cases, the use of deuterons allows higher production yield than protons. METHODS: (186)Re is a ß- emitter which has chemical properties close to the widely used (99m)Tc and has been used in clinical trials for palliation of painful bone metastases resulting from prostate and breast cancer. (186)Re production cross section has been measured between 9 and 23 MeV using the ARRONAX deuteron beam and the stacked-foil technique. A novelty in our work is the use of a monitor foil behind each (nat)W target foil in order to record efficiently the deuteron incident flux and energies all over the stack relying on the International Atomic Energy Agency (IAEA) recommended cross section of the (nat)Ti(d,x)(48)V reaction. Since a good optimization process is supposed to find the best compromise between production yield and purity of the final product, isotope of interest and contaminants created during irradiation are measured using gamma spectrometry. RESULTS: Our new sets of data are presented and compared with the existing ones and with results given by the TALYS code calculations. The thick target yield (TTY) has been calculated after the fit of our experimental values and compared with the IAEA recommended ones. CONCLUSIONS: Presented values are in good agreement with existing data. The deuteron production route is clearly the best choice with a TTY of 7.8 MB/µAh at 30 MeV compared to 2.4 MBq/µAh for proton as projectile at the same energy. The TALYS code gives satisfactory results for (183,186)Re isotopes.

ARRONAX, a high-energy and high-intensity cyclotron for nuclear medicine.

PURPOSE: This study was aimed at establishing a list of radionuclides of interest for nuclear medicine that can be produced in a high-intensity and high-energy cyclotron. METHODS: We have considered both therapeutic and positron emission tomography radionuclides that can be produced using a high-energy and a high-intensity cyclotron such as ARRONAX, which will be operating in Nantes (France) by the end of 2008. Novel radionuclides or radionuclides of current limited availability have been selected according to the following criteria: emission of positrons, low-energy beta or alpha particles, stable or short half-life daughters, half-life between 3 h and 10 days or generator-produced, favourable dosimetry, production from stable isotopes with reasonable cross sections. RESULTS: Three radionuclides appear well suited to targeted radionuclide therapy using beta ((67)Cu, (47)Sc) or alpha ((211)At) particles. Positron emitters allowing dosimetry studies prior to radionuclide therapy ((64)Cu, (124)I, (44)Sc), or that can be generator-produced ((82)Rb, (68)Ga) or providing the opportunity of a new imaging modality ((44)Sc) are considered to have a great interest at short term whereas (86)Y, (52)Fe, (55)Co, (76)Br or (89)Zr are considered to have a potential interest at middle term. CONCLUSIONS: Several radionuclides not currently used in routine nuclear medicine or not available in sufficient amount for clinical research have been selected for future production. High-energy, high-intensity cyclotrons are necessary to produce some of the selected radionuclides and make possible future clinical developments in nuclear medicine. Associated with appropriate carriers, these radionuclides will respond to a maximum of unmet clinical needs.