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http://dx.doi.org/10.22643/JRMP.2022.8.2.139

Cu-64 as a Cancer Theranostics Agent  

Kwang Il Kim (Division of Applied RI, Korea Institute of Radiological & Medical Sciences)
Publication Information
Journal of Radiopharmaceuticals and Molecular Probes / v.8, no.2, 2022 , pp. 139-150 More about this Journal
Abstract
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.
Keywords
Theranostics; $^{64}CuCl_2$; $^{64}Cu$-labeled radiopharmaceuticals; PET;
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1 IAEA Radioisotopes and radiopharmaceuticals Reports No.1. Cyclotron produced radionuclides: Emerging positron emitters for medical applications: 64Cu and 124I. 2016. Available from: https://www-pub. iaea.org/books/IAEABooks/10791/Cyclotron-Produced-Radionu\-clides-Emerging-Positron-Emitters-for-Medical-Applications-64Cu-and-124I.
2 Osredkar J, Sustar N. Copper and zinc, biological role and significance of copper/zinc imbalance. J Clin Toxicol 2011;S3:001.
3 Chellan P, Sadler PJ. The elements of life and medicines. Philos Trans A Math Phys Eng Sci 2015;373(2037):20140182.
4 Cai Z, Anderson CJ. Chelators for copper radionuclides in positron emission tomography radiopharmaceuticals. J Labelled Comp Radiopharm 2014;57(4):224-30.   DOI
5 Chakravarty R, Chakraborty S, Dash A. 64Cu2+ Ions as PET Probe: An Emerging Paradigm in Molecular Imaging of Cancer. Mol Pharm 2016;13(11): 3601-12.   DOI
6 Mercer JF, Camakaris J. Copper comes of age in Melbourne. Metallomics 2016;8(9):816-23.   DOI
7 Burlando B, Evangelisti V, Dondero F, Pons G, Camakaris J, Viarengo A. Occurrence of Cu-ATPase in Dictyostelium: possible role in resistance to copper. Biochem Biophys Res Commun 2002;291(3):476-83.   DOI
8 Montes S, Rivera-Mancia S, Diaz-Ruiz A, Tristan-Lopez L, Rios C. Copper and copper proteins in Parkinson's disease. Oxid Med Cell Longev 2014;2014:147251.
9 Boll MC, Alcaraz-Zubeldia M, Montes S, Rios C. Free copper, ferroxidase and SOD1 activities, lipid peroxidation and NO(x) content in the CSF. A different marker profile in four neurodegenerative diseases. Neurochem Res 2008;33(9):1717-23.   DOI
10 Eum WS, Kang JH. Release of copper ions from the familial amyotrophic lateral sclerosis-associated Cu, Zn-superoxide dismutase mutants. Mol Cell1998:9(1):110-4.
11 Bellingham SA, Lahiri DK, Maloney B, La Fontaine S, Multhaup G, Camakaris J. Copper depletion down-regulates expression of the Alzheimer's disease amyloid-beta precursor protein gene. J Biol Chem 2004;279(19):20378-86.   DOI
12 Hueting R. Radiocopper for the imaging of copper metabolism. J Labelled Comp Radiopharm 2014;57(4):231-8.   DOI
13 Mercer JF, Llanos RM. Molecular and cellular aspects of copper transport in developing mammals. J Nutr 2003;133(5 Suppl 1):1481S-1484S.   DOI
14 Camakaris J, Voskoboinik I, Mercer JF. Molecular mechanisms of copper homeostasis. Biochem Biophys Res Commun 1999;261(2):225-32.   DOI
15 Camakaris J, Petris MJ, Bailey L, Shen P, Lockhart P, Glover TW, Barcroft C, Patton J, Mercer JF. Gene amplification of the Menkes (MNK; ATP7A) P-type ATPase gene of CHO cells is associated with copper resistance and enhanced copper efflux. Hum Mol Genet 1995;4(11):2117-23.   DOI
16 Jalilian AR, Rowshanfarzad P, Sabet M. Preparation of [61Cu]pyruvaldehyde-bis (N4-methylthiosemicarbazone) complex as a possible PET radiopharmaceutical. Radiochim Acta 2006;94:113-7.   DOI
17 Bhargava KK, Gupta RK, Nichols KJ, Palestro CJ. In vitro human leukocyte labeling with 64Cu: an intraindividual comparison with 111In-oxine and 18F- FDG. Nucl Med Biol 2009;36(5):545-9.   DOI
18 Shokeen M, Wadas TJ. The development of copper radiopharmaceuticals for imaging and therapy. Med Chem 2011;7:413-29.   DOI
19 Jiang L, Tu Y, Hu X. Pilot study of 64Cu(I) for PET imaging of melanoma. Sci Rep 2017;31(7):2574.
20 Zhou M, Zhao J, Tian M, Song S, Zhang R, Gupta S, Tan D, Shen H, Ferrari M, Li C. Radio-photothermal therapy mediated by a single compartment nanoplatform depletes tumor initiating cells and reduces lung metastasis in the orthotopic 4T1 breast tumor model. Nanoscale 2015;7(46):19438-47.   DOI
21 Catalogna G, Talarico C, Dattilo V, Gangemi V, Calabria F, D'Antona L, Schenone S, Musumeci F, Bianco C, Perrotti N, Amato R, Cascini GL. The SGK1 kinase inhibitor SI113 sensitizes theranostic effects of the 64CuCl2 in human glioblastoma multiforme cells. Cell Physiol Biochem 2017;43(1):108-19   DOI
22 Righi S, Ugolini M, Bottoni G. Biokinetic and dosimetric aspects of 64CuCl2 in human prostate cancer: possible theranostic implications. EJNMMI Res 2018;8(1):18.
23 Schultze MO, Simmons SJ. The use of radioactive copper in studies on nutritional anemia of rats. J Biol Chem 1942;142:97-106.   DOI
24 Schubert G, Riezler W. Indicator-Untersuchungen mit Radiokupfer beim Menschen; die Absorption parenteral und enteral zugefuhrter Kupferdosen, zugleich Untersuchungen uber die Kreislaufzeit [Indicator examinations with radio-ligands in humans; the absorption of parenterally and enterally supplied copper doses, at the same time studies on the circulation time]. Klin Wochenschr 1947;24:304-6. German.   DOI
25 Peng F, Lu X, Janisse J, Muzik O, Shields AF. PET of human prostate cancer xenografts in mice with increased uptake of 64CuCl2. J Nucl Med 2006;47(10):1649-52.
26 Cai H, Wu JS, Muzik O, Hsieh JT, Lee RJ, Peng F. Reduced 64Cu uptake and tumor growth inhibition by knockdown of human copper transporter 1 in xenograft mouse model of prostate cancer. J Nucl Med 2014;55(4):622-8.   DOI
27 Qin C, Liu H, Chen K, Hu X, Ma X, Lan X, Zhang Y, Cheng Z. Theranostics of malignant melanoma with 64CuCl2. J Nucl Med 2014;55(5):812-7.   DOI
28 Kim KI, Jang SJ, Park JH, Lee YJ, Lee TS, Woo KS, Park H, Choe JG, An GI, Kang JH. Detection of increased 64Cu uptake by human copper transporter 1 gene overexpression using PET with 64CuCl2 in human breast cancer xenograft model. J Nucl Med 2014;55(10):1692-8.   DOI
29 Jorgensen JT, Persson M, Madsen J, Kjaer A. High tumor uptake of 64Cu: implications for molecular imaging of tumor characteristics with copper-based PET tracers. Nucl Med Biol 2013;40(3):345-50.   DOI
30 Ferrari C, Asabella AN, Villano C, Giacobbi B, Coccetti D, Panichelli P, Rubini G. Copper-64 Dichloride as Theranostic Agent for Glioblastoma Multiforme: A Preclinical Study. Biomed Res Int 2015;2015:1-6.
31 Panichelli P, Villano C, Cistaro A, Bruno A, Barbato F, Piccardo A, Duatti A. Imaging of brain tumors with copper-64 chloride: early experience and results. Cancer Biother Radiopharm 2016;31(5):159-67.
32 Avila-Rodriguez MA, Rios C, Carrasco-Hernandez J, Manrique-Aris JC, Martinez-Hernandez R, Garcia-Perez FO, Jalilian AR, Martinez-Rodriguez E, Romero-Pina ME, Diaz-Ruiz A. Biodistribution and radiation dosimetry of [64Cu]copper dichloride: first-in-human study in healthy volunteers. EJNMMI Res 2017;7(1):98.
33 Jin ZH, Furukawa T, Degardin M, Sugyo A, Tsuji AB, Yamasaki T, Kawamura K, Fujibayashi Y, Zhang MR, Boturyn D, Dumy P, Saga T. αVβ3 integrin-targeted radionuclide therapy with 64Cu-cyclam-RAFT-c(-RGDfK-)4. Mol Cancer Ther 2016;15(9):2076-85.   DOI
34 Niccoli Asabella A, Cascini GL, Altini C, Paparella D, Notaristefano A, Rubini G. The copper radioisotopes: a systematic review with special interest to 64Cu. Biomed Res Int 2014;2014:786463.
35 Pfeifer A, Knigge U, Mortensen J, Oturai P, Berthelsen AK, Loft A, Binderup T, Rasmussen P, Elema D, Klausen TL, Holm S, Benzon EV, Hojgaard L, Kjaer A. Clinical PET of neuroendocrine tumors using 64Cu-DOTATATE: first-in-humans study. J Nucl Med 2012;53(8):1207-15.   DOI
36 Sprague JE, Kitaura H, Zou W, Ye Y, Achilefu S, Weilbaecher KN, Teitelbaum SL, Anderson CJ. Noninvasive imaging of osteoclasts in parathyroid hormone.induced osteolysis using a 64Cu-Labeled RGD Peptide. J Nucl Med 2007;48(2):311-8.
37 Ocak M, Beaino W, White A, Zeng D, Cai Z, Anderson CJ. 64Cu-labeled phosphonate cross-bridged chelator conjugates of c(RGDyK) for PET/CT imaging of osteolytic bone metastases. Cancer Biother Radiopharm 2018;33(2): 74-83.
38 Johnbeck CB, Knigge U, Loft A, Berthelsen AK, Mortensen J, Oturai P, Langer SW, Elema DR, Kjaer A. Head-to-head comparison of 64Cu-DOTATATE and 68Ga-DOTATOC PET/CT: a prospective study of 59 patients with neuroendocrine tumors. J Nucl Med 2017;58(3):451-7.   DOI
39 Johnbeck CB, Knigge U, Kjaer A. PET tracers for somatostatin receptor imaging of neuroendocrine tumors: current status and review of the literature. Future Oncol 2014;10(14):2259-77.   DOI
40 Szymanski P, Fraczek T, Markowicz M, Mikiciuk-Olasik E. Development of copper based drugs, radiopharmaceuticals and medical materials. Biometals 2012;25(6):1089-112.   DOI
41 Sasada S, Kurihara H, Kinoshita T, Yoshida M, Honda N, Shimoi T, Shimomura A, Yunokawa M, Yonemori K, Shimizu C, Hamada A, Kanayama Y, Watanabe Y, Fujiwara Y, Tamura K. 64Cu-DOTA-Trastuzumab PET imaging for HER2-specific primary lesions of breast cancer. Ann Oncol 2017;28(8):2028-9.   DOI
42 Arteaga C. Targeting HER1/EGFR: a molecular approach to cancer therapy. Semin Oncol 2003;30(3 suppl 7):3-14.   DOI
43 Mortimer JE, Bading JR, Park JM, Frankel PH, Carroll MI, Tran TT, Poku EK, Rockne RC, Raubitschek AA, Shively JA, Colcher DM. Tumor Uptake of 64Cu-DOTA-trastuzumab in patients with metastatic breast cancer. J Nucl Med 2018;59(1):38-43.   DOI
44 Mortimer JE, Bading JR, Colcher DM, Conti PS, Frankel PH, Carroll MI, Tong S, Poku E, Miles JK, Shively JE, Raubitschek AA. Functional imaging of human epidermal growth factor receptor 2-positive metastatic breast cancer using (64)Cu-DOTA-trastuzumab PET. J Nucl Med 2014;55(1):23-9.   DOI
45 Kurihara H, Hamada A, Yoshida M, Shimma S, Hashimoto J, Yonemori K, Tani H, Miyakita Y, Kanayama Y, Wada Y, Kodaira M, Yunokawa M, Yamamoto H, Shimizu C, Takahashi K, Watanabe Y, Fujiwara Y, Tamura K. (64)Cu-DOTA-trastuzumab PET imaging and HER2 specificity of brain metastases in HER2-positive breast cancer patients. EJNMMI Res 2015;5:8.
46 Ping Li W, Meyer LA, Capretto DA, Sherman CD, Anderson CJ. Receptor-binding, biodistribution, and metabolism studies of 64CuDOTA-cetuximab, a PET-imaging agent for epidermal growth-factor receptor-positive tumors. Cancer Biother Radiopharm 2008;23(2):158-71.
47 Eiblmaier M, Meyer LA, Watson MA, Fracasso PM, Pike LJ, Anderson CJ. Correlating EGFR expression with receptorbinding properties and internalization of 64Cu-DOTA-cetuximab in 5 cervical cancer cell lines. J Nucl Med 2008;49(9):1472-9.   DOI
48 Cai W, Chen K, He L, Cao Q, Koong A, Chen X. Quantitative PET of EGFR expression in xenograft-bearing mice using 64Cu-labeled cetuximab, a chimeric anti-EGFR monoclonal antibody. Eur J Nucl Med Mol Imaging 2007;34(6):850-8.   DOI
49 Carmeliet P, Jain RK. Angiogenesis in cancer and other diseases. Nature 2000;407(6801):249-57.   DOI
50 van Dijk LK, Yim CB, Franssen GM, Kaanders JHAM, Rajander J, Solin O, Gronroos TJ, Boerman OC, Bussink J. PET of EGFR with (64) Cu-cetuximab-F(ab')2 in mice with head and neck squamous cell carcinoma xenografts. Contrast Media Mol Imaging 2016;11(1):65-70.   DOI
51 Zhang Y, Hong H, Orbay H, Valdovinos HF, Nayak TR, Theuer CP, Barnhart TE, Cai W. PET imaging of CD105/endoglin expression with a 61/64Cu-labeled Fab antibody fragment. Eur J Nucl Med Mol Imaging 2013;40(5):759-67.   DOI
52 Zhang Y, Yang Y, Hong H, Cai W. Multimodality molecular imaging of CD105 (Endoglin) expression. Int J Clin Exp Med 2011;4(1):32-42.
53 Dallas NA, Samuel S, Xia L, Fan F, Gray MJ, Lim SJ, Ellis LM. Endoglin (CD105): a marker of tumor vasculature and potential target for therapy. Clin Cancer Res 2008;14(7):1931-7.   DOI
54 Mease RC, Foss CA, Pomper MG. PET imaging in prostate cancer: focus on prostate-specific membrane antigen. Curr Top Med Chem 2013;13(8):951-62.   DOI
55 Afshar-Oromieh A, Hetzheim H, Kratochwil C, Benesova M, Eder M, Neels OC, Eisenhut M, Kubler W, Holland-Letz T, Giesel FL, Mier W, Kopka K, Haberkon U. The theranostic PSMA ligand PSMA-617 in the diagnosis of prostate cancer by PET/CT: biodistribution in humans, radiation dosimetry, and first evaluation of tumor lesions. J Nucl Med 2015;56(11):1697-705.   DOI
56 Grubmuller B, Baum RP, Capasso E, Singh A, Ahmadi Y, Knoll P, Floth A, Righi S, Zandieh S, Meleddu C, Shariat SF, Klingler HC, Mirzaei S. 64Cu-PS-MA-617 PET/CT imaging of prostate adenocarcinoma: first in-human studies. Cancer Biother Radiopharm 2016;31(8):277-86.