IAEA activities to support the member states in the production of targeted alpha therapy radiopharmaceuticals.

Due to the growing interest of International Atomic Energy Agency (IAEA) Member States in implementing targeted radionuclide therapy (TRT) in general, the demand for alpha-emitting radionuclides and radiopharmaceuticals is enormous. As an international platform for peaceful applications of radionuclides, the IAEA has been implementing several activities focusing on the production and quality control of alpha emitters and radiopharmaceuticals as well as capacity building in the field, through Technical Meetings, Workshops, Publications and Conference Supports, IAEA-Coordinated Research Projects (CRP) and Technical Cooperation Program (TC). This review article summarises the IAEA activities on the production and quality control of alpha emitter radiopharmaceuticals for targeted alpha therapy (TAT) and a roadmap to future steps including but not limited to the ongoing CRP on Ac-radiopharmaceuticals.

[Tc]Tc-PSMA-T4-Novel SPECT Tracer for Metastatic PCa: From Bench to Clinic.

Despite significant advances in nuclear medicine for diagnosing and treating prostate cancer (PCa), research into new ligands with increasingly better biological properties is still ongoing. Prostate-specific membrane antigen (PSMA) ligands show great potential as radioisotope carriers for the diagnosis and therapy of patients with metastatic PCa. PSMA is expressed in most types of prostate cancer, and its expression is increased in poorly differentiated, metastatic, and hormone-refractory cancers; therefore, it may be a valuable target for the development of radiopharmaceuticals and radioligands, such as urea PSMA inhibitors, for the precise diagnosis, staging, and treatment of prostate cancer.

Does the Number of Bifunctional Chelators Conjugated to a mAb Affect the Biological Activity of Its Radio-Labeled Counterpart? Discussion Using the Example of mAb against CD-20 Labeled with Y or Lu.

There has been considerable interest in developing a monoclonal antibody (mAb) against-CD-20 (for example, Rituximab) modified by bifunctional chelating agents (BCA) for non-Hodgkin's lymphoma radioimmunotherapy. Therefore, many researchers have modified this monoclonal antibody by attaching different BCA moieties and evaluated their biological activities in terms of in vitro study and in vivo study in healthy and tumor xenografted rodents. This mini-perspective reviews the in vitro studies, the immunoreactivity and physiological distribution studies: organ-to-blood and the tumor-to-organ ratio of conjugates with different numbers of chelators per mAb.

PSMA-D4 Radioligand for Targeted Therapy of Prostate Cancer: Synthesis, Characteristics and Preliminary Assessment of Biological Properties.

A new PSMA ligand (PSMA-D4) containing the Glu-CO-Lys pharmacophore connected with a new linker system (L-Trp-4-Amc) and chelator DOTA was developed for radiolabeling with therapeutic radionuclides. Herein we describe the synthesis, radiolabeling, and preliminary biological evaluation of the novel PSMA-D4 ligand. Synthesized PSMA-D4 was characterized using TOF-ESI-MS, NMR, and HPLC methods.

Impact of DOTA-Chelators on the Antitumor Activity of Lu-DOTA-Rituximab Preparations in Lymphoma Tumor-Bearing Mice.

This work aimed to evaluate the influence of two chelators: DOTA(SCN) and DOTA(NHS) on radioimmunotherapy using Lu-DOTA-Rituximab preparations in murine lymphoma xenograft models. Subsequently, based on animal data, the organ radiation-absorbed doses were extrapolated to humans (adult male). Therapeutic efficacy of Lu-DOTA-Rituximab was evaluated in male nude mice bearing either Raji (B lymphocyte, CD20) and Jurkat (T lymphocyte, CD20) xenografts, utilizing an anti-CD20 antibody-Rituximab conjugate with either DOTA(SCN) or DOTA(NHS).