The objective of the study was to apply the principles of analytical quality by design (AQbD) to the analytical method for the determination of the radiochemical purity (PQR) of the radiopharmaceutical sodium iodide 131I oral solution, by means of thin layer chromatography (TLC) with a Radio-TLC scanner, the same one that allows to evaluate the quality of the product. For the AQbD, the analytical objective profile (ATP), critical quality attributes (CQA), risk management, the method operable design region (MODR) were defined through the response surface methodology for method optimization using the MINITAB ® software, Control Strategy and the validation of the method where the parameters of selectivity, linearity, precision, robustness, detection limit, quantification limit, range and stability of the sample solution were evaluated. Under the experimental conditions, the conditions of the method were demonstrated by TLC-Scanner and optimization was carried out for an injection volume of 3 µL, radioactive concentration of 10 mCi/mL and carrier volume of 40 µL. It was statistically demonstrated that the method is selective for the 131I iodide band Rf of 0,8 and for the radiochemical impurity IO₃⁻ Rf of 0.6, linearity from 6,0 to 22.0 mCi/mL, intermediate precision with Global RSD of 0,624%, robustness with global RSD 0,101%, detection limit of 0,09 mCi/mL, quantification limit of 0.53 Ci/mL, conforming range, and stability of the sample solution evaluated over time 0, 2 and 20 hours with a global RSD of 0,362%, obtaining consistent results. The development of the method based on AQbD allowed the generation of a design space and an operational space with knowledge of all the characteristics and limitations of the method, likewise in all the operations the conformity of the tests to the acceptance criteria was verified. The validity of our method is concluded under the established conditions, suitable for use in the manufacturing process of sodium iodide 131I and application in nuclear medicine services.

Targeted radionuclide therapy is become increasingly prominent as a nuclear medicine subspe-cialty. For many decades, treatment with radionuclides has been mainly restricted to the use of iodine-131 in thyroid disorders. Currently, radiopharmaceuticals, consisting of a radionuclide coupled to a vector that binds to a desired biological target with high specificity, are being de-veloped. The objective is to be as selective as possible at the tumor level, while limiting the dose received at the healthy tissue level. In recent years, a better understanding of molecular mecha-nisms of cancer, as well as the appearance of innovative targeting agents (antibodies, peptides, small molecules) and the availability of new radioisotopes, have enabled considerable advances in the field of vectorized internal radiotherapy with a better therapeutic efficacy, radiation safety and personalized treatments. For instance, targeting the tumor microenvironment, instead of the cancer cells, now appears as particularly attractive. Several radiopharmaceuticals for therapeutic targeting have shown clinical value in severals types of tumors and have been or will soon be approved and authorized for clinical use.

Besides external high-energy photon or proton beam therapy, targeted radionuclide therapy (TRNT) is an alternative approach to deliver radiation to cancer cells. TRNT is distributed within the body by the vascular system and allows targeted irradiation of a primary tumor and all its metastases, resulting in substantially less collateral damage to normal tissues as compared to ex-ternal beam radiotherapy (EBRT). It is a systemic cancer therapy, tackling systemic spread of the disease, which is the cause of death in most cancer patients. The α-emitting radionuclide bis-muth-213 (213Bi) has interesting properties and can be considered as a magic bullet for TRNT. The benefits and drawbacks of targeted alpha therapy with 213Bi are discussed in this review, covering the entire chain from radionuclide production to bedside. First, the radionuclide properties and production of 225Ac and its daughter 213Bi are discussed, followed by the fundamental chemical properties of bismuth. Next, an overview of available acyclic and macrocyclic bifunctional chelators for bismuth, and general considerations for designing a 213Bi-radiopharmaceutical are provided. Finally, we will provide an overview of preclinical and clinical studies involving 213Bi-radiopharmaceuticals, as well as the future perspectives of this promising cancer treatment option.

Kisspeptin (KISS1) and its cognate receptor (KISS1R) are implicated in the progression of various cancers. However, a theranostic radiopharmaceutical targeting the KISS1 receptor (KISS1R) has yet to be explored. A gallium-68 labelled kisspeptin-10 (KP10) has potential as a pan-tumor radiopharmaceutical for the detection of cancers. Furthermore, a lutetium-177 labelled KP10 could find therapeutic application in treating oncological diseases. We attached DOTA to the NH2-terminus of KP10 as we posited that this modification would not impair biological activity and showed that receptor stimulation of inositol phosphate accumulation in HEK293 transfected with the KISS1R gene was similar for KP10 and DOTA-KP10. We describe optimization of radiolabeling with gallium-68 and lutetium-177 and stability in serum, plasma, and whole blood. Pharmacokinetics was established with µPET/CT and ex vivo measurements. Dynamic studies with µPET/CT demonstrated that background clearance for the radiopharmaceutical was rapid with a blood half-life of 18 ± 3 minutes. DOTA-KP10 demonstrated preserved functionality at KISS1R and good blood clearance. These promising results advocate the further development of KP10 structures which have high binding affinity along with proteolytic resistance.