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The pair of copper radionuclides 64 Cu/ 67 Cu (T 1/2 = 12. 7 h/61.8 h) allows, respectively, PET imaging and targeted beta therapy. An analysis of the different production routes of 67 Cu with charged particles was performed and the reaction 70 Zn(d,x) route was identified as a promising one. It may allow the production of 67 Cu without 64 Cu. 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 70 Zn 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 70 Zn target, it is possible to produce high purity 67 Cu 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.

Recent advances in molecular characterization of tumors have allowed identification of new molecular targets on tumor cells or biomarkers. In medical practice, the identification of these biomarkers slowly but surely becomes a prerequisite before any treatment decision, leading to the concept of personalized medicine. Immuno-positron emission tomography (PET) fits perfectly with this approach. Indeed, monoclonal antibodies (mAbs) labelled with radionuclides represent promising probes for theranostic approaches, offering a non-invasive solution to assess in vivo target expression and distribution. Immuno-PET can potentially provide useful information for patient risk stratification, diagnosis, selection of targeted therapies, evaluation of response to therapy, prediction of adverse effects or for titrating doses for radioimmunotherapy. This paper reviews some aspects and recent developments in labelling methods, biological targets, and clinical data of some novel PET radiopharmaceuticals.

Astatine-211 is an alpha emitter that has been identified as a good candidate for targeted alpha therapy. There is an increasing demand on this radionuclide. Very intense beam from linac being put in operation nowadays could be used to meet this demand. This document presents the design exploration of concepts of liquid bismuth targets dedicated to astatine-211 production. Three concepts are presented and analyzed: a capsule, a fluid loop and a windowless fluid loop. Structural and thermal sizing were performed using mechanical Finite Element models (ANSYS Workbench) and Computational Fluid Dynamic models (FLUENT). Production rates were assessed accordingly. Feasibility and expected performances are discussed in conclusion.

Background Radionuclides are the essential component of radiopharmaceuticals, their production needs to consider pharmaceutical regulations and guidelines, also for clinical research applications. Main body In this paper we reflect on the pharmaceutical regulatory landscape for radionuclide production in Europe, with a focus on Good Manufacturing Practices (GMP). The challenges for novel production pathways and the pathways for non-GMP production of radionuclides are discussed. Conclusion In particular when radionuclides are used as starting materials, exemptions from GMP requirements are essential for clinical innovation and a common understanding is needed to enable the safe use of novel radionuclides for medical applications without unnecessary regulatory hurdles for the user.

The development of the so-called theranostics approach, in which imaging information are used to define a personalized therapeutic strategy, is driving the increasing use of radionuclides in nuclear medicine. They are artificially produced either in nuclear reactors, charged particle accelerators, or using radionuclide generators. Each method leads to radioisotopes with different characteristics and then clinical utility. In the first two cases they are extracted from stable or radioactive target bombarded with a particle beam. After extraction/purification of the target, the radionuclides, either implanted on solid or in liquid form, needs to be transported to a centralized production site, a radiopharmacy or an hospital. The transport of needed radioactive material must obey strict rules. For a radionuclide, a limit in activity that it is possible to transport has been established for each type of allowed packages. For type A package these limits are called A1 (for special form sources, i.e., certified perfectly sealed and encapsulated sources) and A2 (for non-special form sources). However, these limits can be easily reached if the activity to transport is high or if the radionuclide of interest is a “non–conventional” one. Indeed, for many radionuclides, there are no available/tabulated A1 and A2 and, in these cases, a very conservative set of values is imposed. This is in particular the case for some of the non-conventional radionuclide of interest in medicine (as for example Tb-149 or Tb-161). The non-tabulated values, and in general the A1/A2 limit, can be evaluated following the so-called Q-system and using Monte Carlo calculations. In the present work, we have used the MCNPX Monte Carlo code to evaluate dose rate values in different exposure scenarios. This has allowed us to determine A1/A2 coefficients for several non-conventional radionuclides of interest for medical applications. The developed technique can be extended easily to other radionuclides and can be adapted in case of changes in regulatory rules.

Among all existing radionuclides, only a few are of interest for therapeutic applications and more specifically for targeted alpha therapy (TAT). From this selection, actinium-225, astatine-211, bismuth-212, bismuth-213, lead-212, radium-223, terbium-149 and thorium-227 are considered as the most suitable. Despite common general features, they all have their own physical characteristics that make them singular and so promising for TAT. These radionuclides were largely studied over the last two decades, leading to a better knowledge of their production process and chemical behavior, allowing for an increasing number of biological evaluations. The aim of this review is to summarize the main properties of these eight chosen radionuclides. An overview from their availability to the resulting clinical studies, by way of chemical design and preclinical studies is discussed.

The scientific community interest in the production of the theranostic 47Sc is due to its medical favourable decay characteristics suitable for both SPECT imaging and therapeutic purposes. Considering the SPES cyclotron, this work is focused on the measurement of the 48/49/50Ti(p,x)47Sc and 46Sc cross sections up to 70 MeV. In fact, 46Sc is the main co-produced contaminant, since it has a longer half-life than the theranostic 47Sc. Enriched 48/49/50Ti powder were deposited on aluminum backing by using the HIVIPP technique and the obtained targets were characterized by Elastic Back Scattering at the INFN-LNL. Experimental data are compared with the scarce literature and the TALYS results, obtained using the default parameters.

Although positron emission tomography (PET) imaging with 18-Fluorodeoxyglucose (18F-FDG) is a promising technique in multiple myeloma (MM), the development of other radiopharmaceuticals seems relevant. CD138 is currently used as a standard marker for the identification of myeloma cells and could be used in phenotype tumor imaging. In this study, we used an anti-CD138 murine antibody (9E7.4) radiolabeled with copper-64 (64Cu) or zirconium-89 (89Zr) and compared them in a syngeneic mouse model to select the optimal tracers for MM PET imaging. Then, 9E7.4 was conjugated to TE2A-benzyl isothiocyanate (TE2A) and desferrioxamine (DFO) chelators for 64Cu and 89Zr labeling, respectively. 64Cu-TE2A-9E7.4 and 89Zr-DFO-9E7.4 antibodies were evaluated by PET imaging and biodistribution studies in C57BL/KaLwRij mice bearing either 5T33-MM subcutaneous tumors or bone lesions and were compared to 18F-FDG-PET imaging. In biodistribution and PET studies, 64Cu-TE2A-9E7.4 and 89Zr-DFO-9E7.4 displayed comparable good tumor uptake of subcutaneous tumors. On the bone lesions, PET imaging with 64Cu-TE2A-9E7.4 and 89Zr-DFO-9E7.4 showed higher uptake than with 18F-FDG-PET. Comparison of both 9E7.4 conjugates revealed higher nonspecific bone uptakes of 89Zr-DFO-9E7.4 than 64Cu-TE2A-9E7.4. Because of free 89Zr’s tropism for bone when using 89Zr-anti-CD138, 64Cu-anti-CD138 antibody had the most optimal tumor-to-nontarget tissue ratios for translation into humans as a specific new imaging radiopharmaceutical agent in MM.

Natural Tl targets were manufactured by electrochemical deposition on a foil gold backing. The electrochemical parameters were defined after several experiments and reverse pulse potential was chosen to avoid the formation of filaments and dendrites. Once these parameters were established, enriched 205Tl targets were manufactured on a gold foil backing to be used to measure the cross sections for 203Pb production by deuteron induced reactions. The production yield was calculated from our excitation functions and was found to be 54 MBq/µAh in the energy interval 32.5 MeV – 30 MeV.

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.