• Nuclear Engineering and Technology
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• 제51권1호
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• pp.269-274
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• 2019

$^{64}Cu$ is a favorable radionuclide in nuclear medicine applications because of its unique characteristics such as three types of decay (electron capture, ${\beta}^-$ and ${\beta}^+$) and 12.7 h half-life. Production of $^{64}Cu$ by irradiation $^{nat}Cu$ and $^{nat}CuNPs$ in Tehran Research Reactor was investigated. The characteristics of copper nanoparticles were investigated with SEM, TEM and XRD analysis. The cross section of $^{63}Cu(n,{\gamma})^{64}Cu$ reaction was done with TALYS-1.8 code. The activity value of $^{64}Cu$ was calculated with theoretical approach and MCNPX-2.6 code. The results were compared with related experimental results which showed good adaptations between them.

• 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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• 제8권2호
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• pp.139-150
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• 2022

Theranostics, a composite word of therapy and diagnosis, is known as personalized medicine and the concept of diagnosis and treatment at the same time. In nuclear medicine, it means performing both therapeutic and diagnostic radioisotope therapy using the same target molecule. The increased production and utilization of ⁶⁴Cu opens a new era of theranostics. The studies introduced here have shown that ⁶⁴CuCl₂ and various compounds or biomolecules labeled with ⁶⁴Cu are unique radiopharmaceuticals with physiological properties suitable for use as diagnostic and therapeutic agents. So far, these two abilities have been described only for radioactive iodine. Although ⁶⁴Cu has complex chemical properties compared to other PET radioisotopes such as ⁶⁸Ga, it has an appropriate half-life and enables high-quality PET images similar to ¹⁸F, which is an advantage in terms of diagnosis. In addition, since it also has therapeutic properties through the release of β^- particles and Auger electrons by electron capture, radiopharmaceuticals using ⁶⁴Cu stand for innovative radiopharmaceuticals for theranostic purposes. Therefore, based on the initial results obtained using ⁶⁴Cu as a therapeutic agent, it is expected that additional research on the application of ⁶⁴Cu will lead to a new era in the theranostics field.

• 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.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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• 제4권2호
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• pp.65-72
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• 2018

Prostate specific membrane antigen (PSMA) is a cell surface membrane protein, which is overexpressed in most prostate cancer. Recently, PET imaging with $[^{68}Ga]$PSMA-HBED-CC has been widely used for the diagnosis of recurrent prostate cancer and the studies on the diagnostic potential of $^{64}Cu$-labeled PSMA ligands reported actively. In this study, we monitored with biological evaluation in vivo and PET imaging of $^{64}Cu$-labeled PSMA ligand ($[^{64}Cu]$PSMA-617). The radiolabelling efficiency and stability of $[^{64}Cu]$PSMA-617 were confirmed by radio-thin layer chromatography. The radiolabeling efficiency of $[^{64}Cu]$PSMA-617 showed over 95%, and stabilities of intact remained over 98% in both human and mouse serum for 48 h. In normal male mice, in vivo uptake of $[^{64}Cu]$PSMA-617 in several organs was measured at 2, 4, 6, 24, 48 h after injection. Rapid blood clearance was observed for $[^{64}Cu]$PSMA-617. The high uptake was observed in the lung, liver, intestines and kidneys at 2 h postinjection, but was low in the other organs (1-2 %ID/g) at 4 h. The dynamic PET/CT images of 22RV1 tumor-bearing nude mice were acquired during 60 min and additionally acquired 24 h and 48 h after injection. In dynamic PET images, $[^{64}Cu]$PSMA-617 uptake ratio in tumors versus muscle was increased as time elaplsed until 60 minutes and remained in tumors at 48 h. In these results, the PET/CT imaging using $[^{64}Cu]$PSMA-617 in prostate cancer 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.

• 한국의학물리학회지:의학물리
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• 제27권2호
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• pp.86-92
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• 2016

디지털 팬텀을 사용한 선량평가 방법은 일반화된 장기에 대해서만 평가가 가능하여 종양에 대한 선량평가가 불가능하다. 이에 본 연구에서는 몸통 팬텀에 방사성동위원소를 주입하고 실제 측정된 CT 영상을 기반으로 장기와 종양에 대하여 몬테카를로 시뮬레이션을 이용하여 S-value를 계산함으로써 장기와 종양에 대한 흡수선량을 평가하고자 하였다. 몸통 팬텀은 폐, 간, 척추, 실린더로 구성되어 있으며 구 모형 팬텀을 이용하여 종양을 모사하였다. 방사성동위원소의 실제 선량 측정은 방사성동위원소 Cu-64 73.85 MBq 주입된 몸통 팬텀에 유리선량계(glass dosimeter)를 삽입하여 방사성동위원소의 선량을 측정하였다. 몬테카를로 시뮬레이션을 위한 몸통 팬텀의 각 영역 정보는 Cu-64가 주입된 몸통 팬텀을 이용하여 PET/CT 영상을 획득하고 CT영상의 해부학적 정보를 우선으로 평균값과 매뉴얼로 각 장기 및 종양을 영역별로 분할하여 제공하였다. 방사성동위원소의 영역별 잔류시간은 PET 영상에서 분할된 영역을 기반으로 시간변화에 따라 Cu-64 방사능량을 측정하여 계산하였다. 각 영역의 S-value는 몬테카를로 시뮬레이션에 입력된 공간상의 좌표, 복셀 크기, 밀도정보를 사용하여 계산하였다. 흡수선량 평가는 몬테카를로 시뮬레이션을 이용하여 선량분포를 계산하였으며 각 영역별로 미치는 S-value와 잔류시간을 이용하여 계산하였다. 각 영역에서의 흡수선량은 간에서 4.52E-02 mGy/MBq, 종양1에서 4.61E-02 mGy/MBq, 그리고 종양2에서 5.98E-02 mGy/MBq으로 평가되었다. 유리선량계로 측정된 선량 값과 시뮬레이션을 통해 계산된 선량 값의 차이는 평균 12.3% 이내의 차이를 보였다. 본 연구결과는 다양한 크기와 위치에 대하여 영상기반 선량평가의 적용가능성을 제시하였다.

• 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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• 제5권1호
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• pp.61-68
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• 2019

Purine type compounds has been recently reported to cause the death for lung cancer cell, related to microtubules-targeting agents (MTAs). Therefore it can be used to develop as theranostic radiopharmceuticals in nuclear medicine or gadolinium-based MRI imaging agents by chelate chemistry. In the study, we tried to chemically bind a DOTA chelate on the end of purine compound and obtained a specific conjugate of DOTA-purine for metal coordination. In particular, radiometal like Cu-64, for the development of MRI imaging agents, can be utilized to choice good candidates before the synthesis of gadolinium complexes. By the screening of radioisotope technique, Gd-DOTA-purine type complex was successfully prepared and showed MRI imaging for lung cancer cell into the mouse model.