• 대한방사성의약품학회지
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• 제7권2호
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• pp.79-84
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• 2021

Radiopharmaceuticals are important for tumor diagnosis and therapy. To deliver a radiotracer at the desired target excluding non-targeted tissues is difficult The development of a targeted tracer that has a good clearance profile while maintaining high biostability and biocompatibility is key to optimizing its biodistribution and transport across biological barriers. Improving the hydrophilicity of radiotracers by PEGylation can reduce serum binding, allowing the tracer to circulate without retention and reducing its affinity for non-targeted tissues. In this study, we synthesized a new benzamido tracer (SnBz-PEG₃₆) with the introduction of a low molecular weight polyethylene glycol unit (PEG₃₆, ~2,100 Da). The tumor targeting efficiency and biodistribution of [¹³¹I]-Bz-PEG₃₆ or radiotracer-loaded liposomes were evaluated after their administration to normal mice or mouse tumor models including CT26 (xenograft) and 4T1 (xenograft and orthotopic). Most of the radiotracer was cleared out rapidly (1-24 h post-administration) through the kidney and there was little tumor uptake.

• 대한방사성의약품학회지
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• 제6권2호
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• pp.155-164
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• 2020

Polyethylene glycol (PEG) has been the most commonly used polymer for the past few decades in the field of biomedical applications due to its gold standard stealth effect. PEGylation of antibody-drug conjugates, liposomes, peptides, nanoparticles, and proteins is done to improve their pharmaceutical efficacy and pharmacokinetic properties. PEGylation of antibodies with various PEG linkers improves targeting ability by increasing the blood circulation time and thus enhances the biodistribution profiles. It also assists in minimizing the immediate capture by the reticuloendothelial system. In this review, we summarize the effect of PEG linkers in an antibody conjugation and their pharmacokinetics in the field of biomedical imaging.

• 대한방사성의약품학회지
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• 제6권2호
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• pp.146-154
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• 2020

Selective installation of proteins using chemical reagents is important for the development of potential biomaterials for the treatment of human diseases. However, modification in a chemo- and regioselective manner under physiological conditions is a great challenge due to the presence of multiple reactive centers in the protein. Currently, the majority of conjugations are limited to lysine (Lys)- and cysteine (Cys)-selective reagents. Thus, they have been extensively studied. Apart from Lys and Cys, widespread site selectivity has been recently achieved through most of the 20 naturally occurring amino acid-bearing reactive functional groups. Consequently, this review focused on several recent achievements in site-selective modification of the rarest amino acid backbones (e.g., methionine, serine, glutamic acid, and tyrosine).

• 대한방사성의약품학회지
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• 제8권1호
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• pp.39-44
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• 2022

The development of methods for the inert and stable radiohalogenation of targeted radiopharmaceuticals is a prerequisite for real-time diagnosis and therapy using radiohalogenated radiopharmaceuticals. Radiohalogenated carboranes demonstrate superior stability in vivo and versatile applications compared with directly labeled tyrosine analogues or synthetically modified organic compounds. Herein, we focus on the most common approaches for the radioiodination (¹²³l, ¹²⁴l, ¹²⁵l, and ¹³¹l) of carborane derivatives.

• BMB Reports
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• 제54권5호
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• pp.266-271
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• 2021

Estrogen-related receptor γ (ERRγ), a member of the orphan nuclear receptor family, is a key mediator in cellular metabolic processes and energy homeostasis. Therefore, ERRγ has become an attractive target for treating diverse metabolic disorders. We recently reported that ERRγ acts as a negative regulator of osteoclastogenesis induced by receptor activator of nuclear factor-κB ligand (RANKL). In the present study, we explored the effects of an ERRγ-specific modulator, GSK5182, on ERRγ-regulated osteoclast differentiation and survival. Interestingly, GSK5182 increased ERRγ protein levels much as does GSK4716, which is an ERRγ agonist. GSK5182 inhibited osteoclast generation from bone-marrow-derived macrophages without affecting cytotoxicity. GSK5182 also attenuated RANKL-mediated expression of cFos and nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), pivotal transcription factors for osteoclastogenesis. Arrested osteoclast differentiation was associated with reduced RANK expression, but not with the M-CSF receptor, c-Fms. GSK5182 strongly blocked the phosphorylation of IκBα, c-Jun N-terminal kinase, and extracellular signal-regulated kinase in response to RANKL. GSK5182 also suppressed NF-κB promoter activity in a dose-dependent manner. In addition to osteoclastogenesis, GSK5182 accelerated osteoclast apoptosis by caspase-3 activation. Together, these results suggest that GSK5182, a synthetic ERRγ modulator, may have potential in treating disorders related to bone resorption.

• 대한방사성의약품학회지
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• 제7권1호
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• pp.33-40
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• 2021

Recently, antibody-drug conjugates (ADCs) are used to deliver efficient cytotoxic payloads selectively in cancer cells. In the designing of an ADC, the antibody is connected to a toxic payload via a covalent linker, which helps to solubilizes the typical hydrophobic payload as well as stabilizes the linkage over circulation. The development of the linkers for the antibody drug conjugate is still in demand. Initially, the acid, disulfide, and cathepsin-sensitive ADCs attracted considerable attention for the delivery of a potent cytotoxic payload but suffer from instability in human and mouse plasma with a short half-life. In addition, It also suffer from a solubility issue that induces aggregation, which is the major problem in their development. ADCs associated with sulfatase and phosphatase cleavable linker are highly soluble due to the anionic nature of sulfate and phosphate groups. The ADCs also showed high stability in human and mouse plasma. Therefore, to overcome these limitations, sulfatase and phosphatase cleavable linkers were developed. This review focuses on the recently reported advantages of sulfatase and phosphatase cleavable linkers for ADCs.

• 대한방사성의약품학회지
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• 제7권2호
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• pp.85-91
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• 2021

Selective amino acid conjugation of bulky antibodies is a valuable asset for real-time diagnosis and therapy. However, selective conjugation incorporating a chelate-bearing radioactive atom into an antibody without affecting its immunoreactivity is a challenging task. A bifunctional chelator (BFC), a selective amino acid-targeting probe, and a linker have been developed to overcome this problem. Here, we report the synthesis of a novel propylene cross-bridged chelator (PCB)-1,8-N,N'-bis-(carboxymethyl)-1,4,8,11-tetraazacyclotetradecane (TE2A)-luminol BFC via a click reaction and radiolabel it with a ⁶⁴Cu ion for tyrosine-selective conjugation of trastuzumab. In the initial optimization study, we tried different oxidative addition conditions such as electro-oxidation, hemin, horseradish peroxidase, iodogen tube, chloramine-T, and iodo beads. In this study, up to 82% of ⁶⁴Cu-PCB-TE2A-luminol was conjugated with the antibody in an iodo bead-catalyzed oxidative addition reaction with an isolated yield of 24.4%.

• 대한방사성의약품학회지
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• 제8권2호
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• pp.151-156
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• 2022

Liposomes are bilayered particles that are surrounded by an aqueous solvent with amphiphilic substances such as phospholipids. Liposomes have the potential to overcome the limitations of physiochemical properties of existing drugs, and are therefore widely used in research for the treatment of many diseases, especially cancer. Currently, there are many liposome manufacturing methods that use various lipids and amphiphiles. Among them, the thin film-hydration method is a traditional and very simple method to prepare liposomes by hydrating a dry lipid film in an aqueous solvent, which has been widely used in the laboratory until recently. Recently, approaches to new nuclear imaging agents and radiotherapy by loading radioactive isotopes inside liposomes have been actively studied. In this review, we would like to discuss considerations for preparing liposomes using the thin film-hydration method.

• 문화기술의 융합
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• 제9권3호
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• pp.1-10
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• 2023

이 연구의 목적은 ANT를 중심으로 창의ˑ융합형 인재 양성 방안을 탐색한 것이다. ANT를 중심으로 창의ˑ융합형 인재를 양성하기 위해서는 첫째, 네트워크 형성단계에서 카오의 법칙을 활용할 필요가 있다. 둘째, 네트워크 형성단계에서 약한 유대의 강한 힘을 활용할 필요가 있다. 셋째, 번역의 4단계 중 문제 제기 단계에서 파문을 일으키기 위해서는 질문하는 능력을 키워야 한다. 넷째, 파문을 던지기 위해서는 다양한 창의적 문제해결 기법 교육이 필요하다. 다섯째, 번역의 4단계 중 2단계인 관심 끌기 단계에서 끼어들기를 성공시키기 위해서는 의사소통 역량과 비판적사고 역량을 교육해야 한다. 후속 연구를 위한 제언은 첫째, ANT에서 제시한 번역의 4단계와 창의적 문제해결 모형단계를 비교 분석해 볼 필요가 있다. 둘째, ANT를 중심으로 구체적인 사례를 적용한 후속 연구들이 있기를 기대한다.

• 대한방사성의약품학회지
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• 제9권1호
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• pp.43-48
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• 2023

For over 50 years, boron neutron capture therapy (BNCT) has been steadily developed for treating various cancers. This is a non-invasive, selective, and targeted radiotherapy wherein boron-rich molecules accumulate at the tumor site. Liposomal vesicles have become a popular and effective drug delivery system for BNCT, with strategies including surface decoration, bilayer integration, and hydrophilic core encapsulation. This review highlights the state-of-the-art uses of liposomes in BNCT and elucidates a new perspective where BNCT can be used with radiotracer guidance in all-in-one delivery systems.