JoVE Logo
Faculty Resource Center

Sign In

Summary

Abstract

Introduction

Protocol

Representative Results

Discussion

Acknowledgements

Materials

References

Medicine

使用64-铜作为示踪剂研究铜相关疾病的正电子发射断层扫描

Published: April 28th, 2023

DOI:

10.3791/65109

1Department of Hepatology and Gastroenterology, Aarhus University Hospital, 2Department of Nuclear Medicine & PET-Center, Aarhus University Hospital

本协议描述了如何在人体中进行 64CuPET / CT和PET / MRI成像,以研究铜相关疾病,例如威尔逊病,以及对铜代谢的治疗效果。

铜是一种必需的微量元素,在生物系统中起到催化和信号传导的作用。几十年来,放射性标记的铜一直被用于研究基本的人类和动物铜代谢和铜相关疾病,如威尔逊病(WD)和门克氏病。该工具包的最新成员是 64 铜 (64Cu) 正电子发射断层扫描 (PET),它将现代计算机断层扫描 (CT) 或磁共振成像 (MRI) 扫描仪的精确解剖成像与 64Cu PET 示踪信号的生物分布相结合。这允许 体内跟踪铜 通量和动力学,从而直接可视化人类和动物铜器官的交通和代谢。因此, 64Cu PET非常适合评估临床和临床前治疗效果,并且已经证明了准确诊断WD的能力。此外, 64项Cu PET / CT研究已被证明在癌症和中风研究等其他科学领域具有价值。本文展示了如何在人体中进行 64Cu PET/CT 或 PET/MR。此处演示了 64Cu 处理、患者准备和扫描仪设置的程序。

铜是一种重要的催化辅助因子,驱动生命所必需的多种重要生化过程,而铜稳态缺陷是人类疾病的直接原因。编码铜转运ATP酶的ATP7A或ATP7B基因突变分别导致Menke和Wilson病。门克氏病 (ATP7A) 是一种罕见的肠道铜过度积累致死性疾病,伴有外周组织严重铜缺乏和铜依赖性酶缺陷1。威尔逊病(WD)(ATP7B)是一种罕见的疾病,其特征是无法将多余的铜排泄到胆汁中,导致铜过载和随后的器官损伤,最严重的是影响肝脏和大脑2

几十年来,对铜代谢的研究一直使用放射性标记的铜(通常是64-铜[64 Cu]或67-铜),这些研究已被证明对于我们了解哺乳动物铜代谢(包括吸收部位和排泄途径)非常宝贵3,456。以前,伽马计数器用于以有限的解剖分辨率检测放射性信号,但最近,64Cu正电子发射断层扫描 (PET) 结合计算机断层扫描 (CT) 或磁共振成像 (MRI) 已被引入人类和动物研究。如今,PET扫描仪具有如此高的灵....

Log in or to access full content. Learn more about your institution’s access to JoVE content here

丹麦中部地区伦理委员会已批准一些使用该 64Cu PET/CT 或 PET/MRI 方案的临床试验 [1-10-72-196-16 (EudraCT 2016-001975-59)、1-10-72-41-19 (EudraCT 2019-000905-57)、1-10-72-343-20 (EudraCT 2020-005832-31)、1-10-72-25-21 (EudraCT 2021-000102-25) 和 1-10-72-15-22 (EudraCT 2021-005464-21)]。在入组时获得参与者的书面知情同意。所有受试者的纳入标准均为>18岁,女性为使用安全避孕措施。威尔逊病患者的排除标准是失代偿性.......

Log in or to access full content. Learn more about your institution’s access to JoVE content here

剂量计算
根据剂量学计算,IV给药的有效放射性剂量为62±5μSv / MBq示踪剂10。因此,根据时间范围,建议使用 50 MBq 剂量。高达 75-80 MBq 适用于较长时间的检查,并提供高质量的图像,而不会超过道德认可的剂量。口服给药的有效剂量为113±1μSv / MBq示踪剂,这是由于示踪剂的肠道蓄积。因此,需要考虑较低的剂量,并且在注射后长达24小时,30 MBq足以产生高质量的?.......

Log in or to access full content. Learn more about your institution’s access to JoVE content here

该方法与任何其他PET方法类似,但12.7小时的长半衰期提供了研究长期铜通量的机会(我们在IV示踪剂注射后长达68小时获得了良好的结果)。协议中的所有步骤都必须由熟悉PET的人员处理,尽管它们并不比任何其他PET检查更关键。

故障 排除
因为我们经常使用 64Cu进行长期研究,所以PET信号会比平时更嘈杂。在量化PET信号时,特别是在胆囊等较小的器官?.......

Log in or to access full content. Learn more about your institution’s access to JoVE content here

由制造商Vilhelm Pedersen&Wife纪念基金会资助。该基金会在研究的规划或任何其他阶段都没有发挥任何作用。

....

Log in or to access full content. Learn more about your institution’s access to JoVE content here

NameCompanyCatalog NumberComments
0.22 micrometer sterilizing filterMerck Life Science
Cannula 21 G 50 mmBD Microlance301155
Cannula 25 G 16 mmBD Microlance300600
Dose calibratorCapintec CRC-PC calibrator
PET/CT scannerSiemens: Biograph
PET/MR scannerGE Signa
PMOD version 4.0PMOD Technologies LLC
Saline solution 0.9% NaClFresenius Kabi
Sodium acetate trihydrate BioUltraSigma Aldrich71188
Solid 64CuCl2Danish Technical University Risø
Sterile waterFresenius Kabi
Venflon 22 G 25 mmBD Venflon Pro Safety393280

  1. Tümer, Z., Møller, L. B. Menkes disease. European Journal of Human Genetics. 18 (5), 511-518 (2010).
  2. Ala, A., Walker, A. P., Ashkan, K., Dooley, J. S., Schilsky, M. L. Wilson's disease. The Lancet. 369 (9559), 397-408 (2007).
  3. Owen, C. A. Absorption and excretion of Cu64-labeled copper by the rat. The American Journal of Physiology-Legacy Content. 207 (6), 1203-1206 (1964).
  4. Osborn, S. B., Roberts, C. N., Walshe, J. M. Uptake of radiocopper by the liver. A study of patients with Wilson's disease and various control groups. Clinical Science. 24, 13-22 (1963).
  5. Vierling, J. M., et al. Incorporation of radiocopper into ceruloplasmin in normal subjects and in patients with primary biliary cirrhosis and Wilson's disease. Gastroenterology. 74 (4), 652-660 (1978).
  6. Gibbs, K., Walshe, J. M. Studies with radioactive copper (64Cu and 67Cu); the incorporation of radioactive copper into caeruloplasmin in Wilson's disease and in primary biliary cirrhosis. Clinical Science. 41 (3), 189-202 (1971).
  7. Kume, M., et al. A semi-automated system for the routine production of copper-64. Applied Radiation and Isotopes: Including Data, Instrumentation and Methods for Use in Agriculture, Industry and Medicine. 70 (8), 1803-1806 (2012).
  8. Ohya, T., et al. Efficient preparation of high-quality 64Cu for routine use. Nuclear Medicine and Biology. 43 (11), 685-691 (2016).
  9. Koole, M., et al. EANM guidelines for PET-CT and PET-MR routine quality control. Zeitschrift für Medizinische Physik. , (2022).
  10. Sandahl, T. D., et al. The pathophysiology of Wilson's disease visualized: A human 64Cu PET study. Hepatology. 76 (6), 1461-1470 (2022).
  11. Munk, D. E., et al. Effect of oral zinc regimens on human hepatic copper content: a randomized intervention study. Scientific Reports. 12 (1), 14714 (2022).
  12. Kjærgaard, K., et al. Intravenous and oral copper kinetics, biodistribution and dosimetry in healthy humans studied by 64Cu]copper PET/CT. EJNMMI Radiopharmacy and Chemistry. 5 (1), 15 (2020).
  13. Brewer, G. J. Zinc acetate for the treatment of Wilson's disease. Expert Opinion on Pharmacotherapy. 2 (9), 1473-1477 (2001).
  14. Bush, J. A., et al. Studies on copper metabolism. XVI. Radioactive copper studies in normal subjects and in patients with hepatolenticular degeneration. Journal of Clinical Investigation. 34 (12), 1766-1778 (1955).
  15. Murillo, O., et al. High value of 64Cu as a tool to evaluate the restoration of physiological copper excretion after gene therapy in Wilson's disease. Molecular Therapy - Methods & Clinical Development. 26, 98-106 (2022).
  16. Squitti, R., et al. Copper dyshomeostasis in Wilson disease and Alzheimer's disease as shown by serum and urine copper indicators. Journal of Trace Elements in Medicine and Biology. 45, 181-188 (2018).

Tags

194

This article has been published

Video Coming Soon

JoVE Logo

Privacy

Terms of Use

Policies

Research

Education

ABOUT JoVE

Copyright © 2024 MyJoVE Corporation. All rights reserved