銅-64

銅-64，⁶⁴Cu
基本
符號	64Cu
名稱	銅-64、Cu-64
原子序	29
中子數	32
CAS号	13981-25-4
核素数据
半衰期	12.701 h ± 0.002 h
衰变产物	64Ni; 64Zn
原子量	63.92976420 u
自旋	1+
衰變模式
衰变类型	衰变能量（MeV）
β-	0.6529
β+	0.5785
	铜的同位素 ; 完整核素表

銅-64（⁶⁴Cu）是銅的正電子和β發射同位素，可用於分子放射治療和正電子發射斷層掃描。對於正電子發射同位素，其異常長的半衰期使其在附著於各種配位基時對PET和PET-CT掃描越來越有用。

性質

⁶⁴Cu的半衰期為12.7小時，其中17.9%透過正電子發射衰變為64Ni，39.0%透過β衰變為64Zn，43.1%透過ε衰變為64Ni，0.475%透過γ輻射/內部轉換。這些輻射分別為β-電子、正電子和γ-電子的0.579 MeV、0.653MeV和1.35MeV。^[2]

生產

銅-64可以透過幾種不同的反應生產，最常見的方法是使用反應器或粒子加速器。熱中子可以透過銅-63（n,γ）銅-64反應產生低比活度（單位物質每秒的衰變次數）、低產量的銅-64。銅-64可在密蘇里大學研究反應器中心（英语：University of Missouri Research Reactor Center）（MURR）使用高能量中子透過鋅-64（n,p）銅-64核反應生成，比活度高，但產量低。利用生物醫學迴旋加速器，鎳-64（p,n）銅-64核反應可以產生大量具有高比活性的核素。^[3]

用途

作為正電子發射體，銅-64已被用於生產用於一系列病症成像的實驗和臨床放射性藥物。它的β輻射也增加了其治療應用的可能性。與典型的PET 放射性核種相比，它的半衰期相對較長，這有利於治療和對某些生理過程進行成像。^[4]^[5]

PET成像

骨轉移

臨床前實驗工作表明，與甲膦酸鹽官能基連接的⁶⁴Cu具有作為PET骨骼影像（英语：PET for bone imaging）試劑的潛力。^[6]

神經內分泌腫瘤(NETs)

神經內分泌腫瘤（NET）在臨床上使用一系列基於DOTA的放射性藥物進行定位。對於PET成像，這些通常是基於鎵-68 的。自2020年起，商業化的⁶⁴Cu-DOTA-TATE產品已被FDA核准用於生長抑素受體陽性NET的國產化。^[7]^[8]

攝護腺癌

鈴蟾肽（英语：Bombesin）已被證明在前列腺癌的BB2受體中過度表達。CB-TE2A是一種穩定的⁶⁴Cu螯合系統，與 Bombesin類似物結合用於前列腺癌的in vitro和in vivo研究。 PET-CT 影像研究表明，它選擇性地被前列腺腫瘤異種移植物攝取，而對非目標組織的攝取減少。其他臨床前研究表明，透過靶向胃泌素釋放肽受體，也可以檢測胰腺癌和乳腺癌。^[9]

腎組織灌流

雙縮氨基硫脲(ETS) 具有作為具有多種銅同位素的 PET 放射性藥物的潛在用途。⁶⁴Cu-ETS 已用於實驗性臨床前心肌、腦和腫瘤灌注評估，腎臟攝取和血流量之間具有線性關係。腎臟灌注也可以用CT或MRI代替PET進行評估，但有缺點：CT需要施用潛在的過敏造影劑。 MRI 避免使用電離輻射，但難以實施，並且經常受到運動偽影的影響。帶有 ⁶⁴Cu 的 PET 可以提供腎灌注的定量測量。^[10]^[11]

肝豆狀核變性

肝豆狀核變性是一種罕見的病症，其中銅在體內過多滯留。銅的有毒水平會導致器官衰竭和過早死亡。⁶⁴Cu已被用於研究患有這種疾病的受試者的全身銅保留。此技術還可以區分雜合子攜帶者和純合子正常人。^[12]

癌症治療

⁶⁴Cu-ATSM – copper(II) (diacetyl-bis (N4-methylthiosemicarbazone)) – is being studied as a possible cancer therapy.

⁶⁴Cu-ATSM（二乙醯基-雙（N4-甲硫基雙縮氨基硫脲））已被證明可以延長荷瘤動物的生存時間。低氧滯留區域已被證明對體外放射治療（英语：External beam radiotherapy）有抵抗力，因為缺氧減少了電離輻射的致命影響。 ⁶⁴Cu因其獨特的腐爛特性而被認為可以殺死這些細胞。在具有或不具有誘導缺氧的結直腸腫瘤的動物模型中，與常氧（英语：Normoxic）細胞相比，缺氧細胞優先吸收Cu-ATSM。結果表明，與對照組相比，該化合物提高了荷瘤倉鼠的存活率。^[13]

參見

參考資料

^ Copper, isotope of mass 64. PubChem. National Center for Biotechnology Information. [25 April 2021] （英语）.
^ Bé, M.-M; Chisté, V; Dulieu, C; Mougeot, X; Chechev, V; Kuzmenko, N; Kondev, F; Luca, A; Galán, M; Nichols, A L; Lee, K B; Arinc, A; Pearce, A; Huang, X; Wang, B. Cu-64 (PDF). Bé, M.-M (编). Table of radionuclides (Volume 6). Sèvres: BIPM. 2006: 13. ISBN 978-92-822-2242-3.
^ Welch, Michael; Redvanly, Carol S. Handbook of Radiopharmaceuticals : radiochemistry and applications. New York: Wiley. 2003. ISBN 9780471495604. S2CID 94079329. doi:10.1002/0470846380.
^ IAEA. Cyclotron Produced Radionuclides: Emerging Positron Emitters for Medical Applications: 64Cu and 124I. Vienna: International Atomic Energy Agency. 2016. ISBN 978-92-0-109615-9 （英语）.
^ Gutfilen, Bianca; Souza, Sergio AL; Valentini, Gianluca. Copper-64: a real theranostic agent. Drug Design, Development and Therapy. 2 October 2018, 12: 3235–3245. PMC 6173185 . PMID 30323557. doi:10.2147/DDDT.S170879 .
^ Sun, Xiankai; Wuest, Melinda; Kovacs, Zoltan; Sherry, Dean; Motekaitis, Ramunas; Wang, Zheng; Martell, Arthur; Welch, Michael; Anderson, Carolyn. In vivo behavior of copper-64-labeled methanephosphonate tetraaza macrocyclic ligands. Journal of Biological Inorganic Chemistry. 1 January 2003, 8 (1–2): 217–225. PMID 12459917. S2CID 22225650. doi:10.1007/s00775-002-0408-5.
^ DETECTNET. Drugs@FDA. Food and Drug Administration. [25 April 2021].
^ Eychenne, Romain; Bouvry, Christelle; Bourgeois, Mickael; Loyer, Pascal; Benoist, Eric; Lepareur, Nicolas. Overview of Radiolabeled Somatostatin Analogs for Cancer Imaging and Therapy. Molecules. 2 September 2020, 25 (17): 4012. PMC 7504749 . PMID 32887456. doi:10.3390/molecules25174012 .
^ Parry, Jesse J.; Andrews, Rebecca; Rogers, Buck E. MicroPET Imaging of Breast Cancer Using Radiolabeled Bombesin Analogs Targeting the Gastrin-releasing Peptide Receptor. Breast Cancer Research and Treatment. 13 July 2006, 101 (2): 175–183. PMID 16838112. S2CID 25579379. doi:10.1007/s10549-006-9287-8.
^ Green, Mark A.; Mathias, Carla J.; Willis, Lynn R.; Handa, Rajash K.; Lacy, Jeffrey L.; Miller, Michael A.; Hutchins, Gary D. Assessment of Cu-ETS2 as a PET radiopharmaceutical for evaluation of regional renal perfusion. Nuclear Medicine and Biology. April 2007, 34 (3): 247–255. PMID 17383574. doi:10.1016/j.nucmedbio.2007.01.002.
^ Welch, Michael J.; Redvanly, Carol S. Handbook of Radiopharmaceuticals: Radiochemistry and Applications. John Wiley & Sons. 2003: 407. ISBN 978-0-471-49560-4 （英语）.
^ Reed, Emily; Lutsenko, Svetlana; Bandmann, Oliver. Animal models of Wilson disease. Journal of Neurochemistry. 2018, 146 (4): 356–373. PMC 6107386 . PMID 29473169. doi:10.1111/jnc.14323 .
^ Lewis, J. S.; Laforest, R.; Buettner, T. L.; Song, S.-K.; Fujibayashi, Y.; Connett, J. M.; Welch, M. J. Copper-64-diacetyl-bis(N4-methylthiosemicarbazone): An agent for radiotherapy. Proceedings of the National Academy of Sciences. 30 January 2001, 98 (3): 1206–1211. Bibcode:2001PNAS...98.1206L. PMC 14733 . PMID 11158618. doi:10.1073/pnas.98.3.1206 .

[1] Copper, isotope of mass 64. PubChem. National Center for Biotechnology Information. [25 April 2021] （英语）.

[BIPM-2] Bé, M.-M; Chisté, V; Dulieu, C; Mougeot, X; Chechev, V; Kuzmenko, N; Kondev, F; Luca, A; Galán, M; Nichols, A L; Lee, K B; Arinc, A; Pearce, A; Huang, X; Wang, B. Cu-64 (PDF). Bé, M.-M (编). Table of radionuclides (Volume 6). Sèvres: BIPM. 2006: 13. ISBN 978-92-822-2242-3.

[welch-3] Welch, Michael; Redvanly, Carol S. Handbook of Radiopharmaceuticals : radiochemistry and applications. New York: Wiley. 2003. ISBN 9780471495604. S2CID 94079329. doi:10.1002/0470846380.

[4] IAEA. Cyclotron Produced Radionuclides: Emerging Positron Emitters for Medical Applications: 64Cu and 124I. Vienna: International Atomic Energy Agency. 2016. ISBN 978-92-0-109615-9 （英语）.

[5] Gutfilen, Bianca; Souza, Sergio AL; Valentini, Gianluca. Copper-64: a real theranostic agent. Drug Design, Development and Therapy. 2 October 2018, 12: 3235–3245. PMC 6173185 . PMID 30323557. doi:10.2147/DDDT.S170879 .

[6] Sun, Xiankai; Wuest, Melinda; Kovacs, Zoltan; Sherry, Dean; Motekaitis, Ramunas; Wang, Zheng; Martell, Arthur; Welch, Michael; Anderson, Carolyn. In vivo behavior of copper-64-labeled methanephosphonate tetraaza macrocyclic ligands. Journal of Biological Inorganic Chemistry. 1 January 2003, 8 (1–2): 217–225. PMID 12459917. S2CID 22225650. doi:10.1007/s00775-002-0408-5.

[7] DETECTNET. Drugs@FDA. Food and Drug Administration. [25 April 2021].

[8] Eychenne, Romain; Bouvry, Christelle; Bourgeois, Mickael; Loyer, Pascal; Benoist, Eric; Lepareur, Nicolas. Overview of Radiolabeled Somatostatin Analogs for Cancer Imaging and Therapy. Molecules. 2 September 2020, 25 (17): 4012. PMC 7504749 . PMID 32887456. doi:10.3390/molecules25174012 .

[9] Parry, Jesse J.; Andrews, Rebecca; Rogers, Buck E. MicroPET Imaging of Breast Cancer Using Radiolabeled Bombesin Analogs Targeting the Gastrin-releasing Peptide Receptor. Breast Cancer Research and Treatment. 13 July 2006, 101 (2): 175–183. PMID 16838112. S2CID 25579379. doi:10.1007/s10549-006-9287-8.

[10] Green, Mark A.; Mathias, Carla J.; Willis, Lynn R.; Handa, Rajash K.; Lacy, Jeffrey L.; Miller, Michael A.; Hutchins, Gary D. Assessment of Cu-ETS2 as a PET radiopharmaceutical for evaluation of regional renal perfusion. Nuclear Medicine and Biology. April 2007, 34 (3): 247–255. PMID 17383574. doi:10.1016/j.nucmedbio.2007.01.002.

[11] Welch, Michael J.; Redvanly, Carol S. Handbook of Radiopharmaceuticals: Radiochemistry and Applications. John Wiley & Sons. 2003: 407. ISBN 978-0-471-49560-4 （英语）.

[12] Reed, Emily; Lutsenko, Svetlana; Bandmann, Oliver. Animal models of Wilson disease. Journal of Neurochemistry. 2018, 146 (4): 356–373. PMC 6107386 . PMID 29473169. doi:10.1111/jnc.14323 .

[lewis-13] Lewis, J. S.; Laforest, R.; Buettner, T. L.; Song, S.-K.; Fujibayashi, Y.; Connett, J. M.; Welch, M. J. Copper-64-diacetyl-bis(N4-methylthiosemicarbazone): An agent for radiotherapy. Proceedings of the National Academy of Sciences. 30 January 2001, 98 (3): 1206–1211. Bibcode:2001PNAS...98.1206L. PMC 14733 . PMID 11158618. doi:10.1073/pnas.98.3.1206 .

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