Separation of 44Sc from Natural Calcium Carbonate Targets for Synthesis of 44Sc-DOTATATE

The rapid increase in applications of scandium isotopes in nuclear medicine requires new efficient production routes for these radioisotopes. Recently, irradiations of calcium in cyclotrons by , deuteron, and proton beams have been used. Therefore, effective post-irradiation separation and preconcentration of the radioactive scandium from the calcium matrix are important to obtain the pure final product in a relatively small volume. Nobias resin was used as a sorbent for effective separation of 44Sc from calcium targets. Separation was performed at pH 3 using a column containing 10 mg of resin. Scandium was eluted with 100 L of 2 mol L1 HCl. Particular attention was paid to the reduction of calcium concentration, presence of metallic impurities, robustness and simple automation. 44Sc was separated with 94.9 2.8% yield, with results in the range of 91.7–99.0%. Purity of the eluate was confirmed with ICP-OES determination of metallic impurities and >99% chelation efficiency with DOTATATE, followed by >36 h radiochemical stability of the complex. A wide range of optimal conditions and robustness to target variability and suspended matter facilitates the proposed method in automatic systems for scandium isotope separation and synthesis of scandium-labeled radiopharmaceuticals

Production of medical Sc radioisotopes with an alpha particle beam

The internal α-particle beam of the Warsaw Heavy Ion Cyclotron was used to produce research quantities of the medically interesting Sc radioisotopes from natural Ca and K and isotopically enriched 42Ca targets. The targets were made of metallic calcium, calcium carbonate and potassium chloride. New data on the production yields and impurities generated during the target irradiations are presented for the positron emitters 43Sc, 44 gSc and 44 mSc. The different paths for the production of the long lived 44 mSc/44 gSc in vivo generator, proposed by the ARRONAX team, using proton and deuteron beams as well as alpha-particle beams are discussed. Due to the larger angular momentum transfer in the formation of the compound nucleus in the case of the alpha particle induced reactions, the isomeric ratio of 44 mSc/44 gSc at a bombarding energy of 29 MeV is five times larger than previously determined for a deuteron beam and twenty times larger than for proton induced reactions on enriched CaCO3 targets. Therefore, formation of this generator via the alpha-particle route seems a very attractive way to form these isotopes. The experimental data presented here are compared with theoretical predictions made using the EMPIRE evaporation code. Reasonable agreement is generally observed

Calcium targets for production of the medical Sc radioisotopes in reactions with p, d or α projectiles

The scandium radioisotopes for medical application can be produced in reactions of calcium with proton, deuteron or alpha projectiles. Enriched isotopic calcium material is commercially available mainly as calcium carbonate which can be used directly for production of Sc radioisotopes or can be converted into other calcium compounds or into metallic form. The superiority of application of calcium oxide is shown throughout analysis of use of each target chemical form

Cyclotron production of 43Sc for PET imaging

Recently, significant interest in 44Sc as a tracer for positron emission tomography (PET) imaging has been observed. Unfortunately, the co-emission by 44Sc of high-energy γ rays (Eγ = 1157, 1499 keV) causes a dangerous increase of the radiation dose to the patients and clinical staff. However, it is possible to produce another radionuclide of scandium—43Sc—having properties similar to 44Sc but is characterized by much lower energy of the concurrent gamma emissions. This work presents the production route of 43Sc by α irradiation of natural calcium, its separation and purification processes, and the labeling of [DOTA,Tyr3] octreotate (DOTATATE) bioconjugate. Methods: Natural CaCO3 and enriched [40Ca]CaCO3 were irradiated with alpha particles for 1 h in an energy range of 14.8–30 MeV at a beam current of 0.5 or 0.25 μA. In order to find the optimum method for the separation of 43Sc from irradiated calcium targets, three processes previously developed for 44Sc were tested. Radiolabeling experiments were performed with DOTATATE radiobioconjugate, and the stability of the obtained 43Sc-DOTATATE was tested in human serum. Results: Studies of natCaCO3 target irradiation by alpha particles show that the optimum alpha particle energies are in the range of 24–27 MeV, giving 102 MBq/μA/h of 43Sc radioactivity which creates the opportunity to produce several GBq of 43Sc. The separation experiments performed indicate that, as with 44Sc, due to the simplicity of the operations and because of the chemical purity of the 43Sc obtained, the best separation process is when UTEVA resin is used. The DOTATATE conjugate was labeled by the obtained 43Sc with a yield >98 % at elevated temperature. Conclusions: Tens of GBq activities of 43Sc of high radionuclidic purity can be obtainable for clinical applications by irradiation of natural calcium with an alpha beam

Badania cyklotronowej produkcji nowych radioizotopów medycznych

Today, radioisotopes are commonly used in medicine, both in diagnosis and therapy.However, steady development of nuclear medicine demands the application of new medicalradioisotopes. The investigation of their possible large-scale production is a first step in along research process before they can be used in clinical trials.In this thesis, the production routes were studied for the formation of medically interesting43Sc, 44m,gSc, 47Sc, 97Ru, and 105Rh with the use of cyclotrons. The scandium radioisotopeswere produced with calcium and titanium targets and proton or deuteron beams; 97Ruwas obtained through the irradiation of molybdenum with particles; and production of105Rh was studied with ruthenium targets and deuteron beam. Two parameters were determinedexperimentally: nuclear reaction cross-section, s(E), and Thick Target Yield, TTY(E),which were used to discuss the possibility of optimal large-scale production conditions ofdiscussed radioisotopes. Additionally, the conversion of s(E) to TTY(E) was automatizedby developing a dedicated software, and anAujourd’hui, les radio-isotopes sont fréquemment utilisés en médecine, pour le diagnosticet la thérapie. Cependant, le développement constant de la médecine nucléaire provoquel’application de nouveaux radio-isotopes médicaux. La recherche sur leur production possibleà grande échelle est la première étape d’un long processus d’études avant de pouvoir deles utilisé dans des essais cliniques.Dans cette thèse, les voies de production ont été étudiées pour la formation de médicalementintéressants 43Sc, 44m,gSc, 47Sc, 97Ru et 105Rh en utilisant de cyclotrons. Les radioisotopesde scandium ont été produits avec des cibles en calcium et en titane et avec desfaisceaux de protons ou de deutérons; 97Ru a été obtenu par irradiation de molybdène avecdes particules ; et la production de 105Rh a été étudiée avec des cibles en ruthénium et avecun faisceau de deutéron. Deux grandeurs ont été déterminés expérimentalement: la sectionefficace de réaction nucléaire, s(E), et l’efficacité de la production, TTY(E), qui ont été utiliséspour discuter des conditions possibles de production optimale à grande échelle de cesradio-isotopes. De plus, la conversion de s(E) en TTY(E) a été automatisée en développantun logiciel spécialisé, et un algorithme de reconstruction de s(E) avec des valuers de TTY(E)a été introduit.Obecnie, radioizotopy sa˛ powszechnie uz˙ywane w medycynie, zarówno do diagnostykijak i do terapii. Jednak cia˛gły rozwój medycyny nuklearnej wymaga zastosowania nowychradioizotopówmedycznych. Poszukiwania ichmoz˙ liwej produkcji na duz˙ a˛ skale˛ to pierwszykrok w długim procesie badan´ , zanim trafia˛ one do prób klinicznych.Wtej rozprawie, zbadano drogi produkcji medycznych radioizotopów 43Sc, 44m,gSc, 47Sc,97Ru oraz 105Rh z u˙zyciem cyklotronów. Radioizotopy skandu zostały wyprodukowane zuz˙yciem tarcz wapiennych i tytanowych oraz wia˛zek protonów i deuteronów; 97Ru byłotrzymany przez aktywacje˛ molibdenu wia˛zka˛ cza˛stek ; natomiast produkcja 105Rh zostałazbadana z uz˙yciemtarcz rutenowych iwia˛zki deuteronów.Dwa parametry zostały zmierzone:przekrój czynny na reakcje˛ ja˛drowa˛, s(E), orazwydajnos´c´ produkcji, TTY(E), które posłuz˙yłydo oszacowaniawarunkówdo optymalnej produkcji badanych radioizotopówna duz˙ a˛ skale˛.Dodatkowo, zautomatyzowano przeliczenie s(E) do TTY(E) za pomoca˛ stworzonego oprogramowania,oraz zaproponowano algorytm rekonstrukcji s(E) na podstawie pomiarówTTY(E)

Recherche sur la production des nouveaux radio-isotopes médicaux par cyclotron

Aujourd’hui, les radio-isotopes sont fréquemment utilises en médecine, pour le diagnostic et la thérapie. Cependant, le développement constant de la médecine nucléaire provoque l’application de nouveaux radio-isotopes médicaux. La recherche sur leur production possible a grande échelle est la première étape d’un long processus d’études avant de pouvoir de les utilise dans des essais cliniques. Dans cette thèse, les voies de production ont été étudiées pour la formation de médicalement intéressants 43Sc, 44m,gSc, 47Sc, 97Ru et 105Rh en utilisant de cyclotrons. Les radioisotopes de scandium ont ete produits avec des cibles en calcium et en titane et avec des faisceaux de protons ou de deuterons; 97Ru a ete obtenu par irradiation de molybdene avec des particules α; et la production de 105Rh a ete etudiee avec des cibles en ruthenium et avec un faisceau de deuteron. Deux grandeurs ont été déterminés expérimentalement: la section efficace de réaction nucleaire, σ(E), et l’efficacité de la production, TTY(E), qui ont été utilisés pour discuter des conditions possibles de production optimale à grande échelle de ces radio-isotopes. De plus, la conversion de σ(E) en TTY(E) a été automatisée en développant un logiciel spécialisé, et un algorithme de reconstruction de σ(E) avec des valeurs de TTY(E) a été introduit.Today, radioisotopes are commonly used in medicine, both in diagnosis and therapy. However, steady development of nuclear medicine demands the application of new medical radioisotopes. The investigation of their possible large-scale production is a first step in a long research process before they can be used in clinical trials. In this thesis, the production routes were studied for the formation of medically interesting 43Sc, 44m,gSc, 47Sc, 97Ru, and 105Rh with the use of cyclotrons. The scandium radioisotopes were produced with calcium and titanium targets and proton or deuteron beams; 97Ru was obtained through the irradiation of molybdenum with α particles; and production of 105Rh was studied with ruthenium targets and deuteron beam. Two parameters were determined experimentally: nuclear reaction cross-section, σ(E), and Thick Target Yield, TTY(E), which were used to discuss the possibility of optimal large-scale production conditions of discussed radioisotopes. Additionally, the conversion of σ(E) to TTY(E) was automatized by developing a dedicated software, and an algorithm for the reconstruction of σ(E) based on TTY(E) measurements was introduced