We report a series of ⁶⁸Ga-labeled hypoxia imaging agents for positron emission tomography (PET) based on mono-, bis- and tri-nitroimidazole conjugates with a bifunctional chelating (BFC) agent 1,4,7-triazacyclononane-1,4,7-tris[methyl(2-carboxyethyl)phosphinic acid] (TRAP). The obtained conjugates were efficiently labeled with ⁶⁸Ga within 10 min at 95℃ with high radiochemical yields (>96 %). The ⁶⁸Ga-labeled derivatives were found to be stable at room temperature in the prepared medium and at 37℃ in human serum up to 4 h. The prepared derivatives were hydrophilic than the standard hypoxia imaging agent, [¹⁸F]FMISO. The development of hydrophilic hypoxia imaging agents are needed to overcome some of the limitations of [¹⁸F]FMISO, such as nonspecific retention in liver and gastrointestinal track. In conclusion, we successfully developed the novel multivalent ⁶⁸Ga labeled nitroimidazole derivatives for hypoxic tissue imaging.

Targeted alpha therapy (TAT) using alpha particle-emitting radionuclides has garnered considerable attention due to its high linear energy transfer (LET) and the selective delivery of isotopes, which minimize collateral damage to surrounding healthy tissues. These unique properties have been substantiated through numerous preclinical and clinical studies, demonstrating the therapeutic efficacy of alpha emitters such as Actinium-225 (²²⁵Ac), Astatine-211 (²¹¹At), and Radium-223 (²²³Ra) in various tumor types. In this study, the cytotoxic effects of ²²⁵Ac, ²¹¹At, and ²²³Ra were systematically evaluated and compared across various human cancer cell lines using the CCK-8 assay and clonogenic assay. The findings provide valuable insights into the cytotoxic mechanisms of alpha-emitters and are anticipated to contribute foundational knowledge for the development and optimization of therapeutic radiopharmaceuticals.

The development and clinical use of radiopharmaceuticals has been rapidly advancing, driven by the increasing demand for diagnostic and therapeutic applications in nuclear medicine. Despite significant progress, the standardization of production technologies and Good Manufacturing Practice (GMP) documentation for radiopharmaceuticals remains a critical challenge, particularly in balancing the needs of developed and developing countries. This study aims to analyze the status and issues in the production and clinical use of medical radioisotopes and radiopharmaceuticals in South Korea, highlight the necessity of standardized production technologies, and propose solutions to enhance GMP compliance and documentation efficiency. Through comprehensive research, including a detailed examination of existing production technologies, quality management processes, and regulatory requirements, we developed standardized guidelines and an IT-based document management system. These solutions are intended to improve production efficiency, ensure regulatory compliance, and ultimately enhance the quality and safety of radiopharmaceuticals.

Boron neutron capture therapy (BNCT) is a precision treatment technology that selectively damages boron-accumulating cells. To apply BNCT to brain tumors, it is essential to develop boron drugs with both high blood-brain barrier (BBB) penetration and tumor-selective accumulation. Additionally, the development of imaging agents capable of visualizing the biodistribution of boron drugs in vivo is critical. In this study, [¹²⁴I]IBTPB was synthesized by radiolabeling the boron-containing benzothiazole compound (BTPB). The tumor selectivity and biodistribution of [¹²⁴I]IBTPB were evaluated to assess its potential as a diagnostic agent for visualizing the in vivo behavior of BTPB using PET imaging. BTPB and [¹²⁴I]IBTPB exhibited differences in their in vivo behavior due to structural differences, administration methods, and dosages. However, these findings provide valuable insights into the challenges that must be addressed in the development of BNCT agents (diagnostics and therapeutics), thereby contributing to the advancement of future BNCT drug development.

Purpose: The objective of this study was to evaluate the estimated radiochemical yield (RCY) and quality of routine [¹⁸F]FDG production over two-year period (2023 to 2024) at Vietnam's Korean cyclotron facility, utilizing the Samyoung Unitech cyclotron (KOTRON-13, 13 MeV) and TRASIS radiosynthesizer (AllInOne 18). Methods: [¹⁸F]Fluoride was generated using a Samyoung Unitech cyclotron, producing up to maximum 2 Ci of [¹⁸F] radioactivity per run, with 10-14 runs conducted weekly. The [¹⁸F]FDG production was carried out using the radiosynthesizer utilizing FDG Dual cassettes through nucleophilic radiofluorination of mannose triflate followed by basic hydrolysis. Quality Controls, including radiochemical purity, radionuclidic purity and identity, chemical purity, residual solvents, bacterial endotoxins, and sterility, were performed in accordance with TCCS 01:2019/HIC Standards using miniGITA TLC Scanner, Mucha MCA, Agilent 1260 GC, Radio-HPLC Agilent 1260 - GINA Star and Endosafe Nexgen-PTS. Facility design and operation were managed in accordance with International Atomic Energy Agency guidelines to ensure GMP-WHO compliance. Results: All quality control tests met the TCCS 01:2019/HIC Standards requirements, ensuring the safety of patient injections. The RCY were within acceptable ranges. The RCY of the second runs was consistently higher than that of the first runs throughout the study period. The RCY for both runs were gradually light decrease, with no significant correlation between cyclotron maintenance and subsequent RCY. Conclusions: Further investigation is needed to identify factors contributing to the decreasing radiochemical yield.

Radioimmunoconjugates, which combine the targeting ability of monoclonal antibodies (mAb) with the therapeutic potential of radioisotopes, hold promise for the treatment of various cancers. However, antibody degradation is a major problem in this field. This degradation can be caused by radiation energy, pH, buffer replacement, or mechanical shaking during the process. In this paper, we address the mechanism involved in antibody degradation, particularly during radiolabeling, and suggest alternatives to overcome these issues.

Neuroendocrine tumors (NETs) are a rare and heterogeneous group of malignancies characterized by the overexpression of somatostatin receptors (SSTRs) which can be targeted for both diagnostic imaging and therapeutic purposes. Radiolabeled somatostatin analogues (SSAs) have become a powerful tool in the theranostic management of these tumors. This review explores recent advancements in radiolabeled SSAs for PET and SPECT imaging, as well as peptide receptor radionuclide therapy (PRRT). It compares well-studied diagnostic radiopharmaceuticals, such as [⁶⁸Ga]Ga-DOTA-TOC, [⁶⁸Ga]Ga-DOTA-TATE and [⁶⁸Ga]Ga-DOTA-NOC, in terms of diagnostic efficacy and tumor uptake potential. Furthermore, this paper explores the potential of PRRT using β-emitters and the emerging use of α-emitters, such as [²²⁵Ac]Ac-DOTA-TOC, along with combination therapies aimed at improving patient outcomes and minimizing side effects.

Mesenchymal-to-epithelial transition factor (c-MET) is a receptor for hepatocyte growth factor (HGF) found in epithelial tissues. It plays a crucial role in cell survival, growth, differentiation, and angiogenesis. In particular, c-MET activation is closely associated with cancer cell migration, invasion, and metastasis, while aberrant HGF/c-MET signaling promotes the progression of various cancers. Based on these findings, various drugs targeting the HGF/c-MET signaling pathway have been developed. This review summarizes the preclinical and clinical evaluations of antibody-based inhibitors, three types of small-molecule c-MET tyrosine kinase inhibitors, and radiopharmaceuticals derived from these drug structures, emphasizing recent advancements in c-MET inhibitors.

Bioorthogonal chemistry defines chemical reactions that selectively occur within living organisms without interacting with other biological processes, establishing itself as a useful tool in the development of radiopharmaceuticals. These reactions are characterized by high selectivity, allowing them to occur selectively between designated molecules and biocompatibility in aqueous conditions. In this review, we explain representative bioorthogonal reactions, such as Copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC), strain-promoted azide-alkyne cycloaddition (SPAAC), the inverse electron demand Diels-Alder reaction (iEDDA) utilizing tetrazine and trans-cyclooctene, and the Staudinger ligation and discuss development of novel radiopharmaceuticals based on these reactions.

In the contemporary medical landscape, international standards for nuclear medicine medical devices occupy a pivotal position. It is of the utmost importance to have international standards for medical devices in place to guarantee patient safety and enhance the precision of diagnosis and treatment. In recent years, new standards have been introduced with the objective of enhancing radiation safety, ensuring data accuracy and optimizing equipment efficiency. Compliance with these standards is a significant factor in maintaining competitiveness in the global medical device market. Furthermore, international collaboration and the exchange of information between regulatory agencies are crucial for the ongoing development and implementation of standards. This study examines the most recent trends in international standard development and analyses the impact of these standards on the development and clinical application of medical devices. Additionally, the study aims to contribute to the direction of future medical device development and the development of standards.