Name: positron emission tomography using 64-copper as a tracer for the study of copper-related disorders
Uploaded: 2023-04-28T12:40:00
Description: Watch this Scientific Journal Video about Positron Emission Tomography Using 64-Copper as a Tracer for the Study of Copper-Related Disorders at JoVE.com

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。

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...

<ol>
	<li>T&#252;mer, Z., M&#248;ller, L. B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Menkes+disease.">Menkes disease.</a> European Journal of Human Genetics. 18 (5), 511-518 (2010).</li><li>Ala, A., Walker, A. P., Ashkan, K., Dooley, J. S., Schilsky, M. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Wilson's+disease.">Wilson's disease.</a> The Lancet. 369 (9559), 397-408 (2007).</li><li>Owen, C. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Absorption+and+excretion+of+Cu64-labeled+copper+by+the+rat.">Absorption and excretion of Cu64-labeled copper by the rat.</a> The American Journal of Physiology-Legacy Content. 207 (6), 1203-1206 (1964).</li><li>Osborn, S. B., Roberts, C. N., Walshe, J. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Uptake+of+radiocopper+by+the+liver.+A+study+of+patients+with+Wilson's+disease+and+various+control+groups.">Uptake of radiocopper by the liver. A study of patients with Wilson's disease and various control groups.</a> Clinical Science. 24, 13-22 (1963).</li><li>Vierling, J. M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Incorporation+of+radiocopper+into+ceruloplasmin+in+normal+subjects+and+in+patients+with+primary+biliary+cirrhosis+and+Wilson's+disease.">Incorporation of radiocopper into ceruloplasmin in normal subjects and in patients with primary biliary cirrhosis and Wilson's disease.</a> Gastroenterology. 74 (4), 652-660 (1978).</li><li>Gibbs, K., Walshe, J. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Studies+with+radioactive+copper+(64Cu+and+67Cu);+the+incorporation+of+radioactive+copper+into+caeruloplasmin+in+Wilson's+disease+and+in+primary+biliary+cirrhosis.">Studies with radioactive copper (64Cu and 67Cu); the incorporation of radioactive copper into caeruloplasmin in Wilson's disease and in primary biliary cirrhosis.</a> Clinical Science. 41 (3), 189-202 (1971).</li><li>Kume, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+semi-automated+system+for+the+routine+production+of+copper-64.">A semi-automated system for the routine production of copper-64.</a> Applied Radiation and Isotopes: Including Data, Instrumentation and Methods for Use in Agriculture, Industry and Medicine. 70 (8), 1803-1806 (2012).</li><li>Ohya, T., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Efficient+preparation+of+high-quality+64Cu+for+routine+use.">Efficient preparation of high-quality 64Cu for routine use.</a> Nuclear Medicine and Biology. 43 (11), 685-691 (2016).</li><li>Koole, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=EANM+guidelines+for+PET-CT+and+PET-MR+routine+quality+control.">EANM guidelines for PET-CT and PET-MR routine quality control.</a> Zeitschrift f&#252;r Medizinische Physik. , (2022).</li><li>Sandahl, T. D., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+pathophysiology+of+Wilson's+disease+visualized:+A+human+64Cu+PET+study.">The pathophysiology of Wilson's disease visualized: A human 64Cu PET study.</a> Hepatology. 76 (6), 1461-1470 (2022).</li><li>Munk, D. E., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effect+of+oral+zinc+regimens+on+human+hepatic+copper+content:+a+randomized+intervention+study.">Effect of oral zinc regimens on human hepatic copper content: a randomized intervention study.</a> Scientific Reports. 12 (1), 14714 (2022).</li><li>Kj&#230;rgaard, K., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Intravenous+and+oral+copper+kinetics,+biodistribution+and+dosimetry+in+healthy+humans+studied+by+64Cu]copper+PET/CT.">Intravenous and oral copper kinetics, biodistribution and dosimetry in healthy humans studied by 64Cu]copper PET/CT.</a> EJNMMI Radiopharmacy and Chemistry. 5 (1), 15 (2020).</li><li>Brewer, G. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Zinc+acetate+for+the+treatment+of+Wilson's+disease.">Zinc acetate for the treatment of Wilson's disease.</a> Expert Opinion on Pharmacotherapy. 2 (9), 1473-1477 (2001).</li><li>Bush, J. A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Studies+on+copper+metabolism.+XVI.+Radioactive+copper+studies+in+normal+subjects+and+in+patients+with+hepatolenticular+degeneration.">Studies on copper metabolism. XVI. Radioactive copper studies in normal subjects and in patients with hepatolenticular degeneration.</a> Journal of Clinical Investigation. 34 (12), 1766-1778 (1955).</li><li>Murillo, O., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=High+value+of+64Cu+as+a+tool+to+evaluate+the+restoration+of+physiological+copper+excretion+after+gene+therapy+in+Wilson's+disease.">High value of 64Cu as a tool to evaluate the restoration of physiological copper excretion after gene therapy in Wilson's disease.</a> Molecular Therapy - Methods &amp; Clinical Development. 26, 98-106 (2022).</li><li>Squitti, R., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Copper+dyshomeostasis+in+Wilson+disease+and+Alzheimer's+disease+as+shown+by+serum+and+urine+copper+indicators.">Copper dyshomeostasis in Wilson disease and Alzheimer's disease as shown by serum and urine copper indicators.</a> Journal of Trace Elements in Medicine and Biology. 45, 181-188 (2018).</li></ol>

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?...

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3，4，5，6。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敏度，可以在注射后长达70小时跟踪64Cu。64Cu的半衰期为12.7小时，可以长期评估铜助焊剂。这种分辨率的提高最近才进入铜研究领域，关于正常和病理性铜代谢的研究，以及评估特定治疗影响的研究，开始出现。此外，具有扩展视野的全身PET扫描仪的引入将进一步提高这些检查的灵敏度。
该方法论文旨在使临床医生和科学家能够在现有的工具库中添加64Cu PET CT / MRI，作为一种强大且易于使用的方法，以核医学部门之间可比的方式评估铜代谢。64铜的生产可以使用不同的方法进行，通常在特殊设施中进行。在核反应中，广泛使用64 Ni（p，n）64 Cu方法，因为在该路线7，8中，低能质子可以获得64Cu的高产率。 生产方法的详细说明超出了本工作的范围，可用性将因国家和地区而异。
在本文中，我们首先描述必要的放射化学和示踪剂的制备。然后，演示了制备PET / CT或PET / MRI扫描仪的原理。

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>0.22 micrometer sterilizing filter</td>
			<td>Merck Life Science</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Cannula 21 G 50 mm</td>
			<td>BD Microlance</td>
			<td>301155</td>
			<td></td>
		</tr>
		<tr>
			<td>Cannula 25 G 16 mm</td>
			<td>BD Microlance</td>
			<td>300600</td>
			<td></td>
		</tr>
		<tr>
			<td>Dose calibrator</td>
			<td>Capintec CRC-PC calibrator</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>PET/CT scanner</td>
			<td>Siemens: Biograph</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>PET/MR scanner</td>
			<td>GE Signa</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>PMOD version 4.0</td>
			<td>PMOD Technologies LLC</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Saline solution 0.9% NaCl</td>
			<td>Fresenius Kabi</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Sodium acetate trihydrate BioUltra</td>
			<td>Sigma Aldrich</td>
			<td>71188</td>
			<td></td>
		</tr>
		<tr>
			<td>Solid 64CuCl2</td>
			<td>Danish Technical University Ris&#248;</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Sterile water</td>
			<td>Fresenius Kabi</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Venflon 22 G 25 mm</td>
			<td>BD Venflon Pro Safety</td>
			<td>393280</td>
			<td></td>
		</tr>
	</tbody>
</table>

positron emission tomography using 64-copper as a tracer for the study of copper-related disorders

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。

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?...

Watch this Scientific Journal Video about Positron Emission Tomography Using 64-Copper as a Tracer for the Study of Copper-Related Disorders at JoVE.com

Positron Emission Tomography Using 64-Copper as a Tracer for the Study of Copper-Related Disorders

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。

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

Copper is an essential trace element, functioning in catalysis and signaling in biological systems. Radiolabeled copper has been used for decades in ...

这种方法已被证明在威尔逊病的研究中具有重要意义，因为我们可以可视化患者的铜分布。铜PET成像的好处在于能够监测其在体内的生物分布，促进各种器官中铜浓度的非侵入性可视化和量化。该技术可用于威尔逊病的诊断和在研究环境中测试治疗效果。将来，该技术还可能用于临床环境中的治疗效果监测，并可能用于铜代谢紊乱的其他疾病。首先，戴上塑料手套。使用长镊子，用消毒棉签彻底消毒铅容器内装有玻璃瓶的示踪剂的橡胶膜。使用镊子将短套管插入膜中，以防止瓶内真空溢出。用镊子将更长的套管插入膜中以吸取示踪剂溶液。将适当大小的塑料注射器插入长套管中，并绘制示踪剂的计算体积。使用镊子，用盖子连接套管以关闭注射器，并小心地将注射器转移到剂量校准器以测量放射性。将其存放在铅容器中直至使用。使用剂量校准器测量注射器中的放射性。记下工作表上的时间和活动。戴上塑料手套，使用无菌镊子小心地从注射器上取下盖子和套管。将注射器连接到患者的静脉通路。记下工作表上的时间。并以稳定的运动注入示踪剂。注射后，从IV通路取出注射器。更换注射器上的盖子和套管，并保持这种状态，直到测量剩余的放射性。用盐水溶液冲洗静脉通路以清除任何残留的示踪剂。再次注意时间。然后测量注射器中存在的剩余放射性并将其记录在工作表上。对于口服给药，这是施用示踪剂的另一种方式，将100毫升亲切倒入一次性软塑料杯中。使用镊子，从注射器中取出盖子和套管。然后戴上塑料手套，小心地将示踪剂注入杯中，不要溢出。将少量的甜酒吸入注射器并将其注射回杯中以确保正确混合。将塑料吸管放入杯子中，然后将杯子交给参与者。记下工作表上的时间。并允许参与者喝混合物。将空杯子、吸管和注射器放入一次性塑料袋中，如果可能，将它们放入铅容器中。记下时间，并用注射器、塑料杯和吸管测量一次性袋子中剩余的放射性。将参与者置于扫描仪的仰卧位置。在开始扫描之前调整扫描仪的位置。进行概述、CT 或 MR 扫描，以计划在 PET 扫描期间要检查的特定区域。在PET扫描协议中，记下抽吸，注射，剩余测量的时间以及抽吸和剩余测量时的放射性水平。将扫描数据下载为DICOM文件，并将其传输到分析程序，如PMOD。调整扫描的色调设置以区分解剖结构。在水平面上工作，定位肝脏和大结构。将适当体积的感兴趣或多个 VOI 放置在肝脏右叶的不同水平面上，以获得最准确的标准摄取值测量值，考虑到该值在右肝叶内可能变化 5%。计算这些需要关注的有机化合物的平均标准摄取值。在一项比较健康受试者和威尔逊病患者的研究中，在注射后 6 小时和 20 小时监测铜的分布。在患者中，铜在肝脏中积聚。而在健康受试者中，铜在具有较高信号的肠道段中可见，表明胆汁铜排泄。64 使用口服示踪剂对两个独立的威尔逊病患者进行铜扫描，有和没有锌治疗。锌治疗可有效减少肠道对铜的吸收，从而降低肝脏中的铜积累。在一个健康的个体中，四周的锌治疗将肝脏中的铜含量降低到治疗前含量的50%左右。切记在放置VOI时在肝脏中寻找大结构。并记住将VOI大小调整为器官大小，以避免其他器官的溢出。该程序可以用动脉血液采样进行拼凑，以便进行动力学分析。除血液外，还可以在尿液和粪便中测量铜-64活性。

Research

JoVE Journal

Medicine

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一项战略，以确定在常见的疾病，如自闭症和精神分裂症的新突变

There are several lines of evidence supporting the role of de novo mutations as a mechanism for common disorders, such as autism and schizophrenia. First, ...

科研

医学

Basic Surgical Techniques in the G&ouml;ttingen Minipig: Intubation, Bladder Catheterization, Femoral Vessel Catheterization, and Transcardial Perfusion

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Biomarkers in an Animal Model for Revealing Neural, Hematologic, and Behavioral Correlates of PTSD

在动物模型揭示神经，血液，创伤后应激障碍和行为相关因素的生物标志物

Identification of biomarkers representing the evolution of the pathophysiology of Post Traumatic Stress Disorder (PTSD) is vitally important, not only for ...

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微型计算机断层扫描成像制备小鼠冠状动脉血管逆行灌注和灌装

Visualization of the vasculature is becoming increasingly important for understanding many different disease states. While several techniques exist for ...

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Quantification of Atherosclerotic Plaque Activity and Vascular Inflammation using [18-F] Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography FDG-PET/CT

动脉粥样硬化斑块的活动和血管炎症的定量使用[18 F]，氟正电子发射断层扫描/电脑断层扫描（FDG-PET/CT）

Conventional non-invasive imaging modalities of atherosclerosis such as coronary artery calcium (CAC)1 and carotid intimal medial thickness (C-IMT)2 ...

Human Neuroendocrine Tumor Cell Lines as a Three-Dimensional Model for the Study of Human Neuroendocrine Tumor Therapy

人类神经内分泌肿瘤细胞株为研究人类神经内分泌肿瘤治疗的三维模型

Neuroendocrine tumors (NETs) are rare tumors, with an incidence of two per 100,&#x200A;000 individuals per year, and they account for 0.5% of all human ...

Non-invasive Imaging and Analysis of Cerebral Ischemia in Living Rats Using Positron Emission Tomography with 18F-FDG

Non-invasive Imaging and Analysis of Cerebral Ischemia in Living Rats Using Positron Emission Tomography with 18F-FDG

无创成像和脑缺血分析生活中的大鼠使用正电子发射断层扫描<sup&gt; 18</sup&gt; F-FDG

Stroke is the third leading cause of death among Americans 65 years of age or older1. The quality of life for patients who suffer from a stroke fails to ...

A Novel in vivo Gene Transfer Technique and in vitro Cell Based Assays for the Study of Bone Loss in Musculoskeletal Disorders

A Novel in vivo Gene Transfer Technique and in vitro Cell Based Assays for the Study of Bone Loss in Musculoskeletal Disorders

一种新型的<em&gt;在体内</em&gt;基因转移技术和<em&gt;在体外</em&gt;细胞分析为肌肉骨骼疾病骨质流失的研究

Differentiation and activation of osteoclasts play a key role in the development of musculoskeletal diseases as these cells are primarily involved in bone ...

Human Brown Adipose Tissue Depots Automatically Segmented by Positron Emission Tomography/Computed Tomography and Registered Magnetic Resonance Images

人类的褐色脂肪组织的仓库的正电子发射断层扫描/计算机断层扫描自动分段及注册磁共振图像

Reliably differentiating brown adipose tissue (BAT) from other tissues using a non-invasive imaging method is an important step toward studying BAT in ...

Using Saccadometry with Deep Brain Stimulation to Study Normal and Pathological Brain Function

使用Saccadometry与深部脑刺激来研究正常和病理脑功能

The oculomotor system involves a large number of brain areas including parts of the basal ganglia, and various neurodegenerative diseases including ...