铜-64

铜-64，⁶⁴Cu
基本
符号	64Cu
名称	铜-64、Cu-64
原子序	29
中子数	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+
衰变模式
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

铜-64（⁶⁴Cu）是铜的正电子和β发射同位素，可用于分子放射治疗和正电子发射断层扫描。对于正电子发射同位素，其异常长的半衰期使其在附著于各种配位基时对PET和PET-CT扫描越来越有用。

性质

⁶⁴Cu的半衰期为12.7小时，其中17.9%透过正电子发射衰变为64Ni，39.0%透过β衰变为64Zn，43.1%透过ε衰变为64Ni，0.475%透过γ辐射/内部转换。这些辐射分别为β-电子、正电子和γ-电子的0.579 MeV、0.653MeV和1.35MeV。^[2]

生产

铜-64可以透过几种不同的反应生产，最常见的方法是使用反应器或粒子加速器。热中子可以透过铜-63（n,γ）铜-64反应产生低比活度（单位物质每秒的衰变次数）、低产量的铜-64。铜-64可在密苏里大学研究反应器中心（英语：University of Missouri Research Reactor Center）（MURR）使用高能量中子透过锌-64（n,p）铜-64核反应生成，比活度高，但产量低。利用生物医学回旋加速器，镍-64（p,n）铜-64核反应可以产生大量具有高比活性的核素。^[3]

用途

作为正电子发射体，铜-64已被用于生产用于一系列病症成像的实验和临床放射性药物。它的β辐射也增加了其治疗应用的可能性。与典型的PET 放射性核种相比，它的半衰期相对较长，这有利于治疗和对某些生理过程进行成像。^[4]^[5]

PET成像

骨转移

临床前实验工作表明，与甲膦酸盐官能基连接的⁶⁴Cu具有作为PET骨骼影像（英语：PET for bone imaging）试剂的潜力。^[6]

神经内分泌肿瘤(NETs)

神经内分泌肿瘤（NET）在临床上使用一系列基于DOTA的放射性药物进行定位。对于PET成像，这些通常是基于镓-68 的。自2020年起，商业化的⁶⁴Cu-DOTA-TATE产品已被FDA核准用于生长抑素受体阳性NET的国产化。^[7]^[8]

摄护腺癌

铃蟾肽（英语：Bombesin）已被证明在前列腺癌的BB2受体中过度表达。CB-TE2A是一种稳定的⁶⁴Cu螯合系统，与 Bombesin类似物结合用于前列腺癌的in vitro和in vivo研究。 PET-CT 影像研究表明，它选择性地被前列腺肿瘤异种移植物摄取，而对非目标组织的摄取减少。其他临床前研究表明，透过靶向胃泌素释放肽受体，也可以检测胰腺癌和乳腺癌。^[9]

肾组织灌流

双缩氨基硫脲(ETS) 具有作为具有多种铜同位素的 PET 放射性药物的潜在用途。⁶⁴Cu-ETS 已用于实验性临床前心肌、脑和肿瘤灌注评估，肾脏摄取和血流量之间具有线性关系。肾脏灌注也可以用CT或MRI代替PET进行评估，但有缺点：CT需要施用潜在的过敏造影剂。 MRI 避免使用电离辐射，但难以实施，并且经常受到运动伪影的影响。带有 ⁶⁴Cu 的 PET 可以提供肾灌注的定量测量。^[10]^[11]

肝豆状核变性

肝豆状核变性是一种罕见的病症，其中铜在体内过多滞留。铜的有毒水平会导致器官衰竭和过早死亡。⁶⁴Cu已被用于研究患有这种疾病的受试者的全身铜保留。此技术还可以区分杂合子携带者和纯合子正常人。^[12]

癌症治疗

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

⁶⁴Cu-ATSM（二乙酰基-双（N4-甲硫基双缩氨基硫脲））已被证明可以延长荷瘤动物的生存时间。低氧滞留区域已被证明对体外放射治疗（英语：External beam radiotherapy）有抵抗力，因为缺氧减少了电离辐射的致命影响。 ⁶⁴Cu因其独特的腐烂特性而被认为可以杀死这些细胞。在具有或不具有诱导缺氧的结直肠肿瘤的动物模型中，与常氧（英语：Normoxic）细胞相比，缺氧细胞优先吸收Cu-ATSM。结果表明，与对照组相比，该化合物提高了荷瘤仓鼠的存活率。^[13]

参见

参考资料

^ 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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