Functionalized NaA Nanozeolites Labeled with 224,225Ra for Targeted Alpha Therapy

The 223Ra, 224Ra, and 225Ra radioisotopes exhibit very attractive nuclear properties for application in radionuclide therapy. Unfortunately the lack of appropriate bifunctional ligand for radium is the reason why these radionuclides have not found application in receptor-targeted therapy. In the present work, the potential usefulness of the NaA nanozeolite as a carrier for radium radionuclides has been studied. 224Ra and 225Ra, a-particle emitting radionuclides, have been absorbed in the nanometer-sized NaA zeolite (30–70 nm) through simple ion exchange. 224,225Ra-nanozeolites exhibited very high stability in solutions containing physiological salt, EDTA, amino acids, and human serum. To make NaA nanozeolite particles dispersed in water their surface was modified with a silane coupling agent containing poly(ethylene glycol) molecules. This functionalization approach let us covalently attach a biomolecule to the NaA nanozeolite surface.JRC.E.5-Nuclear chemistr

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

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

Radiobioconiugates labeled with Auger electron emitters in targeted radionuclide therapy

In contrast to the radiation therapy methods, that use an external ion beam source, the internal radiotherapy is performed by the direct administration of radionuclides conjugated to a targeting vector. Crucial criteria for the use of radiopharmaceuticals at a selective localization and retention in the tumor lesion are biological or biochemical differences between tumor and non-tumor tissue. Auger electron emitters that can target cancer cells are an attractive agents for internal radiation therapy. Besides of a emitters, radionuclides that decay with the emission of very low energy Auger electrons are well suited for the treatment of small tumors, micrometastases or residual tumor after surgical resection of a primary lesion. In contrast to a radiation, however, Auger emitters have low toxicity when decaying outside the cell during blood transport and they are therefore interesting candidates for targeted radionuclide therapy. However, due to nanometers range of Auger electrons the challenge is to target cancer cells specifically and achieve intracellular and intranuclear uptake for maximum DNA damage. So far, no system has been developed to allow for selective delivery of the Auger electron emitter to the cancer cell and next delivering it to cell nucleus, near the DNA strand. An overview of Auger radiation therapy approaches of the past decade shows several research directions and various targeting vehicles. The latter include small molecules, aptamers, hormones, halogenated nucleotides, peptides oligonucleotides and monoclonal antibodies and their fragments. In present article we discuss the basic principles of Auger electron therapy as compared with targeted α and β radionuclide therapy, characteristic of used Auger emitters and briefly the main advantages and disadvantages of the different targeting modalities that are under investigation