• 대한방사성의약품학회지
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• 제3권2호
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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.

• 대한방사성의약품학회지
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• 제8권1호
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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.

• 대한방사성의약품학회지
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• 제8권2호
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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.

• 대한방사성의약품학회지
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• 제3권2호
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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.

• 대한방사성의약품학회지
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• 제1권1호
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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.

• 대한방사성의약품학회지
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• 제3권2호
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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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• 제41권4호
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• pp.326-334
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• 2007

에스트로젠 수용체 양성 유방암에서 과발현되는 에스트로젠 수용체는 $[^{18}F]FES$와 같은 $^{18}F$이 표지된 스테로이드계 에스트로젠 수용체 리간드를 사용하여 양전자방출단층촬영기로 영상을 얻을 수 있다. 반감기가 12.7시간인 $^{64}Cu$에 비해 1.8시간인 $^{18}F$은 반감기가 짧고, $^{64}Cu$로 표지 하는 경우보다 수율이 낮은 단점이 있다. 사이클렌은 구리, 인듐, 갈륨, 가돌리륨 등과 같은 금속과 안정한 착물을 형성한다. 이를 근거로 2개의 페놀 하이드록시 그룹을 가지고 있는 사이클렌을 기본구조로 한 구리 착물을 합성하였다. 재료 및 방법 : 1,7 위치에 보호기를 가지고 있는 1,7-bis(benzyloxy-carbonyl)-cyclen은 기존에 알려진 방법에 따라 합성 되어졌다. 여기에 4,10 위치에 2개의 4-benzyloxybenzyl groups을 도입한 후, Pd/C상에서의 수소화 반응으로 benzyloxycarbonyl과 benzyl groups이 모두 제거됨으로써 1,7-bis(4-hydroxybenzyl)-cyclen (1)을 성공적으로 합성할 수 있었다. 결과: 우리가 합성한 물질 1은 $^1H,\;^{13}C-NMR$ 그리고 질량분석기로 만들어졌는지 여부를 확인하였다. 이 물질들은 구리 이온과 반응하여 $[Cu(1)]^{2+}2(ClO_4)^-$와 $[Cu(1)Cl]^+Cl^-$를 형성하였고, 고분해능 FAB 질량분석기로 확인하였다. 결론: 우리는 질소원자에 trans 방향으로 2개의 페놀 그룹을 가지고 있는 cyclen 유도체를 합성하는데 성공하였고, 구리이온과 반응하여 각각 전체 전하가 +2그리고 +1인 구리 착물을 합성하였으며, 이들은 에스트로젠 수용체의 영상화를 위한 PET 추적자로 쓰일 수 있는 가능성이 있다.

• 대한방사성의약품학회지
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• 제9권1호
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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.

• 한국식품영양과학회지
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• 제32권1호
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• pp.96-101
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• 2003

본 연구는 시중에 유통되고 있는 칼슘강화식품의 칼슘, 마그네슘, 나트륨, 칼륨, 철, 구리, 아연 등 무기질을 분석하여 칼슘함량의 표시실태를 파악하고 칼슘 및 다른 무기질의 흡수에 미치는 영향을 각 무기질간의 비율로 알아보고자 하였다. 각 식품군 별 칼슘표시량과 분석 값의 오차값의 중앙값과 범위는 곡류가공품이 164.4%(116.3~343.9%), 라면류는 148.4% (87.2~180.9%), 레토르트식품은 37.0%(109.0~157.7%), 음료류는 102.6%(65.48~159.8%)였다. 그리고 칼슘이외의 다량 무기질의 함량은 인이 곡류가공품 100 g당 105.0 mg(46.7~164.8mg), 라면류는 92.5 mg(53.0~128.5mg), 레토르트식품은 36.6 mg(27.6~39.7 mg), 음료류는 11.5 mg(ND~99.0 mg)이었으며 마그네슘의 함량은 곡류가공품이 17.8mg(10.3~32.7 mg) 이었고 라면류가 17.13 mg(14.5~20.9 mg), 레토르트식품은 9.9 mg(6.8~15.7 mg), 음료류는 6.5 mg (0.2~15.3 mg)였다. 나트륨은 곡류가공품의 100 g 당 313.7 mg(36.0~626.6 mg)을 함유했으며, 라면류에는 581.9 mg(306.6~899.0 mg), 레토르트식품에는 455.8 mg(374.7~518.5 mg), 음료류에는 10.74 mg(2.45~85.4 mg)이 있었고 칼륨은 곡류가공품에 65.72 mg(ND~305.10 mg), 라면류에 119.98 mg(99.53~140.52 mg), 레토르트식품에 100.81 mg(67.67~135.70 mg), 음료류에 55.47 mg(0.72~181.50 mg)를 포함하는 것으로 나타났다. 미량 무기질 중에서 철은 곡류가공품 100 g 중 2.70 mg(0.63~3.98 mg), 라면에 1.78 mg(1.03~2.49 mg), 레토르트식품은 0.97 mg(0.64~8.54 mg), 음료류는 0.14 mg(0.14~0.19 mg)이었고, 구리는 곡류가공품은 0.17 mg(0.08~0.22 mg), 라면류는 0.16 mg(0.14~0.19 mg), 레토르트식품은 0.08 mg(0.05~0.13 mg), 음료류는 0.01 mg(0.01~0.11 mg)이었으며 아연은 각각 0.55 mg(0.19~0.77 mg), 0.35 mg(0.28~0.45 mg), 0.40 mg(0.33~0.59 mg), 0.06 mg(0.01~0.37 mg)으로 나타났다. 칼슘에 대한 각 무기질 간의 비율을 살펴보면 Ca : Fe 분자량비의 평균$\pm$표준편차는 곡류가공품이 126.33$\pm$44.36, 라면류가 130.65$\pm$34.67, 레토르트식품은 120.31$\pm$71.15, 음료류가 700.25$\pm$553.70이었고, Ca : P 중량비가 각각 2.63$\pm$1.99, 1.79$\pm$0.39, 2.80$\pm$0.53, 8.35$\pm$12.87이었으며, Ca : Mg 중량비는 각각 11.86$\pm$540, 9.29$\pm$1.34, 9.09$\pm$2.09, 32.50$\pm$41.35이었다. 칼슘과 마그네슘의 흡수에 영향을 미치는 P : Mg 분자량비는 곡류가공품이 4.11$\pm$1.54, 라면류가 4.17$\pm$0.67, 레토르트식품은 2.58$\pm$0.45, 음료류는 2.59$\pm$2.50으로 나타났다. 위의 연구결과에서 볼 때 시료의 93.0%가 실제측정값이 표시량의 80% 이상이어야 한다는 식품 등의 표시기준에 적합하였으나(14), 표시량에 대한 분석값의 오차범위가 65.48~343.9%로 넓어서 칼슘의 함량영양표시가 소비자에게 올바른 정보를 제공하고 있지 못하고 있었다. 그러므로 제조업체에서 품질관리를 보다 철저히 해야 할 것이며. 정부에서는 영양성분 표시량에 맞추어 식품을 섭취하는 소비자들이 자신이 생각한 것보다 훨씬 과잉 섭취하는 일이 없도록 표시기준의 허용오차 상한선 설정을 추진해야 할 것으로 생각된다. 그리고 일반 가공식품에 칼슘을 첨가할 때는 칼슘의 흡수뿐 아니라 다른 무기질의 흡수 및 이용성을 좋게 하기 위해 다른 무기질과 균형을 맞추어 첨가량을 결정하여 칼슘강화로 소비자들이 최대한의 효과를 얻고 다른 무기질과의 균형도 잃지 않도록 관리하여야 할 것이다.