• Journal of Radiopharmaceuticals and Molecular Probes
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• v.3 no.2
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• pp.59-64
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• 2017

It has been reported that $^{64}Cu$ was radiolabeled with bombesin (BBN) peptide binding to the gastrin releasing peptide receptor expressed in human prostate cancer cells (PC3), confirming tumor target efficacy in mouse model. In this study, we developed the kit for the diagnosis and treatment of prostate cancer that can be used clinically using bombesin peptide available of $^{64}Cu$ and $^{177}Lu$ radioisotope labeling. The NODAGA-galacto-BBN peptide containing the NODAGA chelator and galactose was dispensed into a sterilized glass vial and lyophilized to prepare a kit. The stability of the kit after long-term storage in the $4^{\circ}C$ cold chamber and the radiolabeling efficiency after $^{64}Cu$ or $^{177}Lu$ labeling were confirmed by thin layer chromatography. When labeling with $^{64}Cu$ at the initial stage of storage, labeling efficiency of NODAGA-galacto-BBN peptide kit was over 96%, labeling efficiency was over 90% when $^{177}Lu$ was labeled. At 11 months after storage, the radiolabeling efficiency of kit against $^{64}Cu$ and $^{177}Lu$ was each over 95% and 90%. The cell viability was significantly reduced in the $^{177}Lu$-NODAGA-galacto-BBN treated group compared with the control and $^{177}Lu$ alone treated group in clonogenic assay. In conclusion, the NODAGA-galacto-BBN kit prepared by the lyophilization showed high stability over time and high yield of radioisotope labeling. Also $^{177}Lu$-NODAGA-galacto-BBN confirmed high cytotoxicity to prostate cancer cells. Therefore, the NODAGA-galacto-bombesin kit is expected to be useful for the diagnosis and treatment of prostate cancer patients.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.8 no.1
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• pp.45-49
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• 2022

With the development of monoclonal antibodies, therapeutic or diagnostic radioisotope has been successfully delivered at tumor sites with high selectivity for antigens. Different approaches have been applied to improve the tumor-to-normal ratio by considering the in vivo stability of radioimmunoconjugates as a prerequisite. Various stable and inert antibody radiolabeling techniques for radioimmunoconjugate preparation have been extensively evaluated to enhance in vivo stability. Antibody radiolabeling techniques should be rapid and easy; they should not disrupt the immunoreactivity and in vivo behavior of antibodies, which are coupled with a bifunctional chelator (BFC) to stably coordinate with a radiometal. For the design of BFCs, radiometal coordination properties must be considered. However, various diagnostic radionuclides, such as ⁸⁹Zr, ⁶⁴Cu, ⁶⁸Ga, ¹¹¹ln, and ^99mTc, or therapeutic radionuclides, such as ¹⁷⁷Lu, ⁶⁷Cu, ⁹⁰Y, and ²²⁵Ac, have been increasingly used for antibody radiolabeling. In addition to useful radionuclides, ⁶⁴Cu and ¹⁷⁷Lu with the most accessible or the highest production rates in many countries should be considered. In this review, we mainly discussed antibody radiolabeling techniques and conditions that involve ⁶⁴Cu and ¹⁷⁷Lu radiometals.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.8 no.2
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• pp.77-85
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• 2022

The Td05 and Sgc8c, DNA-based aptamers, are well-known to target internalized surface markers (IGHM and PTK7) of Burkitt's lymphoma and acute lymphoblastic leukemia (ALL). Thus, Td05 and Sgc8c labeled with metallic radioisotope ⁶⁴Cu can be evaluated as potential diagnostic PET imaging agents. In this study, we modified the carbon chain length of the last adenosine of aptamer (n = 3, 6, 12) to increase tumor cell uptake and select the best candidate among six types of aptamer analogues and one adenosine of aptamer. After labeling of ⁶⁴Cu, [⁶⁴Cu]Cu-DOTA-aptamer analogues were evaluated in vitro studies (serum stability, Log P values, cell uptake, biodistribution). Then, we evaluate in vivo PET imaging study for two candidates (⁶⁴Cu-DOTA-C12-Sgc8c, ⁶⁴Cu-DOTA-C6-Td05). PET images clearly visualize tumors at 24 h post-injection rather than at an early time point and the tumor-to-background ratio also increases at the delay time point. ⁶⁴Cu-DOTA-C12-Sgc8c and ⁶⁴Cu-DOTA-C6-Td05 could be used as potential radiotracers for lymphoma.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.3 no.2
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• pp.103-112
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• 2017

The combination of nanoparticle with radioisotope could give the in vivo information with high sensitivity and specificity. However, radioisotope labeling of nanoparticle is very difficult and radioisotopes have different physicochemical properties, so the radioisotope selection of nanoparticle should be carefully considered. $^{18}F$ was first option to be considered for labeling of nanoparticle. For the labeling of $^{18}F$ with nanoparticle, Prosthetic group is widely used. Iodine, another radioactive halogen, is often used. Since radioiodine isotopes are various, they can be used for different imaging technique or therapy in the same labeling procedures. $^{99m}Tc$ can easily be obtained as pertechnatate ($^{99m}{TcO_4}^-$) by commercial generator. Ionic $^{68}Ga$ (III) in dilute HCl solution is also obtained by generator system, but $^{68}Ga$ can be substituted for $^{67}Ga$ because of the short half-life (67.8 min). $^{64}Cu$ emits not only positron but also ${\beta}-particle$. Therefore $^{64}Cu$ can be used for imaging and therapy at the same time. These radioactive metals can be labeled with nanoparticle using the bifunctional chelator. $^{89}Zr$ has longer half-life (78.4 h) and is used for the longer imaging time. Unlike different metals, $^{89}Zr$ should use the other chelate such as DFO, 3,4,3-(LI-1,2-HOPO) or DFOB.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.1 no.1
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• pp.23-30
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• 2015

Radioisotopes emitting low-range highly ionizing radiation such as ${\beta}$-particles are of increasing significance in internal radiotherapy. Among the ${\beta}$-particle emitting radioisotopes, $^{67}Cu$ is an attractive radioisotope for various nuclear medicine applications due to its medium energy ${\beta}$-particle, gamma emissions, and 61.83-hour half-life, which can also be used with $^{64}Cu$ for PET imaging. The production and application of the ${\beta}$-emitting radioisotope $^{67}Cu$ for therapeutic radiopharmaceutical are outlined, and different production routes are discussed. A survey of copper chelators used for antibody labeling is provided. It has been produced via proton, alpha, neutron, and gamma irradiations followed by solvent extraction, ion exchange, electrodeposition. Clinical studies using $^{67}Cu$-labelled antibodies in lymphoma, colon carcinoma and bladder cancer patients are reviewed. Widespread use of this isotope for clinical studies and preliminary treatments has been limited by unreliable supplies, cost, and difficulty in obtaining therapeutic quantities.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.3 no.2
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• pp.54-58
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• 2017

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry(MALDI-TOF MS) is one of the powerful methods that enable analysis of small molecules as well as large molecules up to about 500,000 Da without severe fragmentation. MALDI-TOF MS, thus, has been a very useful an analytical tool for the confirmation of synthetic molecules, probing PTMs, and identifying structures of a given protein. In recent nuclear medicine, MALDI-TOF MS liner ion mode helps researcher calculate the average number of chelator(or linkage) per an antibody conjugate, such as DOTA-(or DFO-) trastuzumab for labeling a medical radioisotope. This simple technique can be utilized to improve the labeling method and control the quality at the development of antibody-based radiopharmaceuticals, which is very effected to diagnosis and therapy for in vivo tumor cells, with radioisotopes like $^{89}Zr$, $^{64}Cu$, and 177Lu. To minimize the error, MALDI-TOF MS measurement is repeatedly performed for each sample in this study, and external calibration is carried out after data collection.

• Nuclear Medicine and Molecular Imaging
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• v.41 no.4
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• pp.326-334
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• 2007

Purpose: The estrogen receptor (ER), which is over-expressed in ER-positive breast tumors, has been imaged by positron emission tomography (PET) using $[^{18}F]$ labeled estrogen ligands, especially $[^{18}F]FES$. However, $[^{18}F]$ has relatively short-lived half-life ($t_{1/2}$ =1.8 h) and the labeling yield of radio-fluorination is usually low compared with $^{64}Cu\;(t_{1/2}=12.7\;h)$. 1,4,7,10-tetraazacyclododecane (cyclen) is used to form stable metal complexes with copper, indium, gallium, and gadolinium. With these in mind, we prepared cyclen-based Cu complexes which mimic estradiol in aspect of two hydroxyl groups. Materials and Methods: 1.7-Protected cyclen, 1.7-bis (benzyloxycarbonyl)-cyclen was synthesized according to the reported procedure. After introducing two 4-benzyloxybenzyl groups at 4,10-positions, the benzyloxycarbonyl and benzyl groups were removed at the same time by hydrogenation on Pd/C to give 1,7-bis(4-hydroxybenzyl)-1,4,7,10-tetraazacyclododecane (1). Results: The prepared ligand 1 was fully characterized by $^1H,\;^{13}C$ NMR, and mass spectrometer. The synthesized ligand was reacted with copper chloride and copper perchlorate to give copper complexes $[Cu(1)]^{2+}2(CIO_4^-)\;and\;[Cu(1)Cl]^+Cl^-$ which were confirmed by high-resolution mass (FAB). Conclusion: We successfully synthesized a cyclen derivative of which two phenol groups are located on trans position of N-atoms. And, two Cu(ll) complexes of +2 and +1 overall charge, were prepared as a potential PET tracers for ER imaging.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.9 no.1
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• pp.23-33
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• 2023

Prostate cancer ranks as the world's second most frequently diagnosed cancer among men, and is responsible for the fifth highest number of cancer-related deaths in this population. The development of effective diagnostic and therapeutic approaches for prostate cancer remains a major challenge in the field of oncology. Over the past few years, the prostate-specific membrane antigen (PSMA) has raised as a hopeful tracer for the diagnosis and treatment of prostate cancer.Various radioisotopes, such as ¹³¹I, ^99mTc, ⁶⁸Ga, and ¹⁷⁷Lu, have been used to label PSMA analogues, with varying degrees of success. Among these, ⁶⁸Ga-PSMA-11 and ¹⁷⁷Lu-PSMA-617 have emerged as the most promising radioligands for clinical use. Recently, researchers have been exploring the use of other radioisotopes, such as ²¹¹At, ⁸⁹Zr, ^64/67Cu, and ^203/212Pb, for the labeling of PSMA-targeted radioligands. These radioisotopes have unique properties that may offer advantages over existing radioligands, such as longer half-lives, higher specific activities, and different emission profiles. Efforts are currently underway to develop these radiopharmaceuticals and make them more widely available for clinical use. These exciting developments highlight the potential of PSMA-targeted radioligands for the diagnosis and treatment of prostate cancer, and provided significant implications for the management of this disease in the future. The current study aims to provide a comprehensive summary of the latest research and clinical applications of radiolabeled PSMA inhibitors for diagnoses and therapy of prostate cancer, emphasizing the exciting developments in the field and their potential impact on clinical practice.

• Journal of the Korean Society of Food Science and Nutrition
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• v.32 no.1
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• pp.96-101
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• 2003

This study was done to analyze the contents of minerals, to compare the measured values of calcium and the labeled values in food labeling and to analyze the ratio of calcium to other minerals in 43 calcium-fortified Food products sold in markets in Seoul, Korea. Content of minerals such as Ca, P, Mg, Na, K, Fe, Cu, Zn was measured by atomic absorption or colorimetric method after dry-ashing or wet-ashing. The measured values of calcium were ranged 65.5~343.9% of the labeled values in 43 calcium-fortified products. In 21 calcium-fortified food products, the measured calcium values were ranged 120～160% of the labeled values, and in three drinks those were less than 80% of the labeled, which is not acceptable to the food regulation. The ratios of Ca:P were 2.63$\pm$1.99 (mean$\pm$SD) in grain Products, 1.79$\pm$0.39 in Ramyuns, 2.80$\pm$0.53 in retort pouch food products and 8.35$\pm$12.87 in drinks. The Ca:Fe ratios were 126.33$\pm$44.36 in grain products, 130.65$\pm$34.67 in Ramyuns, 120.31$\pm$71.15 in retort pouch food products and 700.25$\pm$553.70 in drinks. The ratios of Ca:Mg were 11.86$\pm$5.40 in grain products, 9.29$\pm$1.34 in Ramyuns, 9.09$\pm$2.09 in retort pouch food products and 32.50$\pm$41.35 in drinks. The P:Mg ratios were 4.11$\pm$1.54 in grain products, 4.17$\pm$0.67 in Ramyuns, 2.58$\pm$0.45 in retort pouch food Products and 2.59$\pm$2.50 in drinks. These results suggest calcium contents and the ratio of calcium contents to other minerals in calcium-fortified food products should be strictly controlled.