• Title/Summary/Keyword: Cu-64

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Cu-64 as a Cancer Theranostics Agent

  • Kwang Il Kim
    • Journal of Radiopharmaceuticals and Molecular Probes
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    • v.8 no.2
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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.

Modeling and experimental production yield of 64Cu with natCu and natCu-NPs in Tehran Research Reactor

  • Karimi, Zahra;Sadeghi, Mahdi;Ezati, Arsalan
    • Nuclear Engineering and Technology
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    • v.51 no.1
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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.

Intratumoral distribution of 64Cu-ATSM and 18F-FDG in VX2tumor xenografted rabbit

  • Yoo, Ran Ji;Lee, Ji Woong;Lee, Kyo Chul;An, Gwang Il;Ko, In Ok;Chung, Wee Sup;Park, Ji Ae;Kim, Kyeong Min;Choi, Yang-Kyu;Kang, Joo Hyun;Lim, Sang Moo;Lee, Yong Jin
    • Journal of Radiopharmaceuticals and Molecular Probes
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    • v.1 no.2
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    • pp.123-129
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    • 2015
  • $^{64}Cu$-labeled diacetyl-bis($N^4$-methylthiosemicarbazone) is a promising agent for internal radiation therapy and imaging of hypoxic tissues. In the study, we confirmed hypoxia regions in VX2 tumor implanted rabbits with injection $^{64}Cu$-ATSM and $^{18}F$-FDG using positron emission tomography (PET)/computed tomography (CT). PET images with $^{18}F$-FDG and $^{64}Cu$-ATSM were obtained for 40 min by dynamic scan and additional delayed PET images of $^{64}Cu$-ATSM the acquired up to 48 hours. Correlation between intratumoral $O_2$ level and $^{64}Cu$-ATSM PET image was analyzed. $^{64}Cu$-ATSM and $^{18}F$-FDG were intravenously co-injected and the tumor was dissected and cut into slices for a dual-tracer autoradiographic analysis. In the PET imaging, $^{64}Cu$-ATSM in VX2 tumors displayed a specific uptake in hypoxic region for48 h. The uptake pattern of $^{64}Cu$-ATSM in VX2 tumor at 24 and 48 h did not match to the $^{18}F$-FDG. Through ROI analysis, in the early phase (dynamic scan), $^{18}F$-FDG has positive correlation with $^{64}Cu$-ATSM but late phase (24 and 48 h) of the $^{64}Cu$-ATSM showed negative correlation with $^{18}F$-FDG. High uptake of $^{64}Cu$-ATSM in hypoxic region was responded with significant decrease of oxygen pressure, which confirmed by $^{64}Cu$-ATSM PET imaging and autoradiographic analysis. In conclusion, $^{64}Cu$-ATSM can utilize for specific targeting of hypoxic region in tumor, and discrimination between necrotic- and viable hypoxic tissue.

Development & Assessment of Alkyl Chain Modified Aptamers as Potential PET Radiotracers for Lymphoma Diagnosis

  • Ji Woong Lee;Un Chol Shin;Seok u Bae;Ji Yoon Kim;Hae joon Cho;Ji Ae Park;Kyo Chul Lee;Jung Young Kim;Suhng Wook Kim
    • 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.

Synthesis and evaluation of 64Cu-labeled avidin for lymph node imaging

  • Kang, Choong Mo;Kim, Hyunjung;Lee, Yong Jin;Choe, Yearn Seong
    • Journal of Radiopharmaceuticals and Molecular Probes
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    • v.5 no.1
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    • pp.54-60
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    • 2019
  • Sentinel lymph node (SLN) imaging plays an important role in surgery of patients with breast cancer and melanoma. In this study, avidin (Av), a tetrameric protein glycosylated with mannose and N-acetylglucosamine molecules, was labeled with $^{64}Cu$ and then evaluated for LN imaging. $^{64}Cu$-Labeled $NeutrAvidin^{TM}$ (NAv), a non-glycosylated form of Av, was used for comparison. 1,4,7,10-Tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA)-conjugated Av and NAv were prepared from the corresponding proteins and DOTA-NHS ester, which were then labeled with copper-64 and purified using PD-10 columns. The numbers of DOTA molecules conjugated to Av and NAv were 4.9 and 3.3, respectively. [$^{64}Cu$]Cu-DOTA-conjugated Av and NAv were prepared in 93% and 73% radiochemical yields, respectively. In vitro serum stability study showed that copper-64 remained stable on all radiotracers for 24 h (>97%). MicroPET/CT images showed that high radioactivity was accumulated in LNs within 15 min after footpad-injection of radiotracers. Tissue distribution data of mice demonstrated significantly higher uptake in the popliteal (PO) LN than lumbar (LU) LN for $^{64}Cu$-labeled Av (relative % ID/g excluding the injection sites: 66.2% and 26.0%, respectively) compared with those of $^{64}Cu$-labeled NAv (43.0% and 49.2%, respectively). The results of this study suggest that mannose molecules on Av enabled the radiotracer to retain in the first LN after mouse footpad-injection.

Synthesis and biological evaluation of diagnostic reagent for prostate cancer using copper-64 radioisotope

  • Ahn, Heesu;Kim, Mi Hyun;Han, Sang Jin;Woo, Sang Keun;Kim, Jung Young;Lee, Kyu Chul;Lim, Il Han;Lee, Yong Jin
    • Journal of Radiopharmaceuticals and Molecular Probes
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    • v.4 no.2
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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.

Effect of filters and reconstruction method on Cu-64 PET image

  • Lee, Seonhwa;Kim, Jung min;Kim, Jung Young;Kim, Jin Su
    • Journal of Radiopharmaceuticals and Molecular Probes
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    • v.3 no.2
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    • pp.65-71
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    • 2017
  • To assess the effects of filter and reconstruction of Cu-64 PET data on Siemens scanner, the various reconstruction algorithm with various filters were assessed in terms of spatial resolution, non-uniformity (NU), recovery coefficient (RC), and spillover ratio (SOR). Image reconstruction was performed using filtered backprojection (FBP), 2D ordered subset expectation maximization (OSEM), 3D reprojection algorithm (3DRP), and maximum a posteriori algorithms (MAP). For the FBP reconstruction, ramp, butterworth, hamming, hanning, or parzen filters were used. Attenuation or scatter correction were performed to assess the effect of attenuation and scatter correction. Regarding spatial resolution, highest achievable volumetric resolution was $3.08mm^3$ at the center of FOV when MAP (${\beta}=0.1$) reconstruction method was used. SOR was below 4% for FBP when ramp, Hamming, Hanning, or Shepp-logan filter were used. The lowest NU (highest uniform) after attenuation & scatter correction was 5.39% when FBP (parzen filter) was used. Regarding RC, 0.9 < RC < 1.1 was obtained when OSEM (iteration: 10) was used when attenuation and scatter correction were applied. In this study, image quality of Cu-64 on Siemens Inveon PET was investigated. This data will helpful for the quantification of Cu-64 PET data.

Model-based predictions for nuclear excitation functions of neutron-induced reactions on 64,66-68Zn targets

  • Yigit, M.;Kara, A.
    • Nuclear Engineering and Technology
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    • v.49 no.5
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    • pp.996-1005
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    • 2017
  • In this paper, nuclear data for cross sections of the $^{64}Zn(n,2n)^{63}Zn$, $^{64}Zn(n,3n)^{62}Zn$, $^{64}Zn(n,p)^{64}Cu$, $^{66}Zn(n,2n)^{65}Zn$, $^{66}Zn(n,p)^{66}Cu$, $^{67}Zn(n,p)^{67}Cu$, $^{68}Zn(n,p)^{68}Cu$, and $^{68}Zn(n,{\alpha})^{65}Ni$ reactions were studied for neutron energies up to 40 MeV. In the nuclear model calculations, TALYS 1.6, ALICE/ASH, and EMPIRE 3.2 codes were used. Furthermore, the nuclear data for the (n,2n) and (n,p) reaction channels were also calculated using various cross-section systematics at energies around 14-15 MeV. The code calculations were analyzed and obtained using the different level densities in the exciton model and the geometry-dependent hybrid model. The results obtained from the excitation function calculations are discussed and compared with literature experimental data, ENDF/B-VII.1, and the TENDL-2015 evaluated data.

CU Depth Decision Based on FAST Corner Detection for HEVC Intra Prediction (HEVC 화면 내 예측을 위한 FAST 에지 검출 기반의 CU 분할 방법)

  • Jeon, Seungsu;kim, Namuk;Jeon, Byeungwoo
    • Journal of Broadcast Engineering
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    • v.21 no.4
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    • pp.484-492
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    • 2016
  • The High efficiency video coding (HEVC) is the newest video coding standard that achieves coding efficiency higher than previous video coding standards such as H.264/AVC. In intra prediction, the prediction units (PUs) are derived from a large coding unit (LCU) which is partitioned into smaller coding units (CUs) sizing from 8x8 to 64x64 in a quad-tree structure. As they are divided until having the minimum depth, Optimum CU splitting is selected in RDO (Rate Distortion Optimization) process. In this process, HEVC demands high computational complexity. In this paper, to reduce the complexity of HEVC, we propose a fast CU mode decision (FCDD) for intra prediction by using FAST (Features from Accelerated Segment Test) corner detection. The proposed method reduces computational complexity with 53.73% of the computational time for the intra prediction while coding performance degradation with 0.7% BDBR is small compared to conventional HEVC.