• Nuclear Engineering and Technology
• /
• v.51 no.1
• /
• pp.269-274
• /
• 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.

• Journal of Radiopharmaceuticals and Molecular Probes
• /
• v.1 no.1
• /
• pp.23-30
• /
• 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
• /
• v.8 no.2
• /
• pp.139-150
• /
• 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.

• Journal of Radiopharmaceuticals and Molecular Probes
• /
• v.8 no.2
• /
• pp.77-85
• /
• 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
• /
• v.3 no.2
• /
• pp.59-64
• /
• 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
• /
• v.4 no.2
• /
• pp.65-72
• /
• 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.

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

• Progress in Medical Physics
• /
• v.27 no.2
• /
• pp.86-92
• /
• 2016

An absorbed dose calculation method using a digital phantom is implemented in normal organs. This method cannot be employed for calculating the absorbed dose of tumor. In this study, we measure the S-value for calculating the absorbed dose of each organ and tumor. We inject a radioisotope into a torso phantom and perform Monte Carlo simulation based on the CT data. The torso phantom has lung, liver, spinal, cylinder, and tumor simulated using a spherical phantom. The radioactivity of the actual absorbed dose is measured using the injected dose of the radioisotope, which is Cu-64 73.85 MBq, and detected using a glass dosimeter in the torso phantom. To perform the Monte Carlo simulation, the information on each organ and tumor acquired using the PET/CT and CT data provides anatomical information. The anatomical information is offered above mean value and manually segmented for each organ and tumor. The residence time of the radioisotope in each organ and tumor is calculated using the time activity curve of Cu-64 radioactivity. The S-values of each organ and tumor are calculated based on the Monte Carlo simulation data using the spatial coordinate, voxel size, and density information. The absorbed dose is evaluated using that obtained through the Monte Carlo simulation and the S-value and the residence time in each organ and tumor. The absorbed dose in liver, tumor1, and tumor2 is 4.52E-02, 4.61E-02, and 5.98E-02 mGy/MBq, respectively. The difference in the absorbed dose measured using the glass dosimeter and that obtained through the Monte Carlo simulation data is within 12.3%. The result of this study is that the absorbed dose obtained using an image can evaluate each difference region and size of a region of interest.

• Journal of Radiopharmaceuticals and Molecular Probes
• /
• v.3 no.2
• /
• pp.103-112
• /
• 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
• /
• v.5 no.1
• /
• pp.61-68
• /
• 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.