查看“︁钆喷酸”︁的源代码

{{Drugbox
| Verifiedfields = changed
| Watchedfields = changed
| verifiedrevid = 476997570
| image = Gd(DTPA)(aq)2-.png
| image2 = Gadolinium-Diethylentriaminpentaacetat.svg
| synonyms = Gd-DTPA、SHL-451A<Br>gadopentetate dimeglumine（磁显葡胺）

<!--Clinical data-->
| tradename = Magnevist（马根维显）
| Drugs.com = {{drugs.com|CDI|gadopentetate_dimeglumine}}
| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
| pregnancy_category = 
| routes_of_administration = [[静脉注射]]
| ATC_prefix = V08
| ATC_suffix = CA01
| ATC_supplemental =

<!-- Legal status -->
| legal_AU = <!-- Unscheduled / S2 / S4 / S8 -->
| legal_UK = <!-- GSL / P / POM / CD -->
| legal_US = Rx-only
| legal_CN = 处方药
| legal_US_comment =
| legal_EU = Rx-only
| legal_EU_comment =
| legal_status =

<!--Pharmacokinetic data-->
| bioavailability = 
| protein_bound = 
| metabolism = 
| elimination_half-life = 分布半衰期：12分钟<br>清除半衰期：100分钟
| excretion =

<!--Identifiers-->
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 86050-77-3
| PubChem = 6857474
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB00789
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 50087
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = RH248G8V27
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D01707
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 31797
| ChEMBL_Ref = {{ebicite|changed|EBI}}
| ChEMBL = 1200431

<!--Chemical data-->
| C=14 | H=18 | Gd=1 | N=3 | O=10
| smiles = [Gd+3].[O-]C(=O)CN(CCN(CC(=O)O)CC([O-])=O)CCN(CC([O-])=O)CC(=O)O.O[C@H]([C@@H](O)CNC)[C@H](O)[C@H](O)CO.O[C@@H](CNC)[C@@H](O)[C@H](O)[C@H](O)CO
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C14H23N3O10.2C7H17NO5.Gd/c18-10(19)5-15(1-3-16(6-11(20)21)7-12(22)23)2-4-17(8-13(24)25)9-14(26)27;2*1-8-2-4(10)6(12)7(13)5(11)3-9;/h1-9H2,(H,18,19)(H,20,21)(H,22,23)(H,24,25)(H,26,27);2*4-13H,2-3H2,1H3;/q;;;+3/p-3/t;2*4-,5+,6+,7+;/m.00./s1
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = LGMLJQFQKXPRGA-VPVMAENOSA-K
|drug_name=|alt=|caption=|type=|MedlinePlus=|licence_EU=|licence_US=}}

'''钆喷酸'''（[[国际非专有药名|INN]]：gadopentetic acid）,化学式：C<sub>14</sub>H<sub>18</sub>GdN<sub>3</sub>O<sub>10</sub>，为Ga<sup>3+</sup>与{{le|二乙三胺五乙酸|Pentetic acid}}（DTPA）的螯合物，因此可表示为'''Ga-DTPA'''。为首个用于临床的[[磁共振成像]]（MRI）造影剂，商品名为'''马根维显'''（Magnevist）<ref name = "进展">{{cite journal |author1=潘博 |title=核磁共振成像对比增强造影剂的研究进展 |journal=世界最新医学信息文摘 |date=2016 |volume=16 |issue=30 |pages=38-39 |doi=10.3969/j.issn.1671-3141.2016.30.023}}</ref>。

临床上采用其葡甲胺盐形式进行注射给药，即'''钆喷酸葡胺'''（USAN：gadopentetate dimeglumine，钆喷酸二葡甲胺）（旧称'''磁显葡胺'''<ref>{{cite journal |author1=张冬,冯晓源,王从俭 |title=磁显葡胺含量测定方法的建立 |journal=中国医学计算机成像杂志 |date=2005 |issue=1 |pages=65-67 |doi=10.19627/j.cnki.cn31-1700/th.2005.01.016}}</ref>）。其在[[血腦屏障|血脑屏障]]破裂处和血管、血流动力学方面具有较高的灵敏度<ref>{{cite journal |author1=M Aschner, JL Aschner |title=Manganese transport across the blood-brain barrier: relationship to iron homeostasis |url=https://archive.org/details/sim_brain-research-bulletin_1990-06_24_6/page/857 |journal=Brain research bulletin |date=1990 |volume=24 |issue=6 |pages=857-860 |doi=10.1016/0361-9230(90)90152-P}}</ref>，同时也是目前临床最常用的核磁共振成像造影剂之一<ref name= "造影剂书">{{cite book |author1=何国祥 |author2=王毅翔 |title=造影剂药理学及临床应用 |date=2002 |publisher=上海科学技术出版社 |location=上海 |isbn=7532362264}}</ref><ref>{{cite journal |author1=于兆臻，黄建雨，周赞民，李晓伟 |title=核磁共振成像造影剂的发展现状 |journal=山东化工 |date=2019 |volume=48 |issue=21 |pages=60-62+67 |doi=10.19319/j.cnki.issn.1008-021x.2019.21.023}}</ref>。

==历史==
钆喷酸由1981年德国先灵(Schering AG)制药公司的Hanns-Joachim Weinmann和其同事首次发现<ref>{{Cite patent | country = US | number = 5021236 | url=https://patents.google.com/patent/US5021236|title = Method of enhancing NMR imaging using chelated paramagnetic ions bound to biomolecules}}</ref> ，1983年Weinmann与Brasch首次应用于脑部肿瘤诊断，1987年通过美国[[FDA]]认证<ref>{{cite journal |author1=H Yim, SG Yang, YS Jeon, IS Park, M Kim, DH Lee, YH Bae, K Na |title=The performance of gadolinium diethylene triamine pentaacetate-pullulan hepatocyte-specific T1 contrast agent for MRI |journal=Biomaterials |date=2011 |volume=32 |issue=22 |pages=5187-5194 |doi=10.1016/j.biomaterials.2011.03.069}}</ref>，同时开启了MRI造影剂的研究历程<ref name = "进展"/>。

2017年7月，因为长期使用钆喷酸会造成钆脑部沉积，[[欧洲药品管理局]]建议其成员国暂停批准包括马根维显在内的线性结构钆造影剂用于全身使用。<ref>''European Medicines Agency: Gadolinium-containing contrast agents ''[http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/referrals/Gadolinium-containing_contrast_agents/human_referral_prac_000056.jsp&mid=WC0b01ac05805c516f ema.europa.eu] {{Wayback|url=http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/referrals/Gadolinium-containing_contrast_agents/human_referral_prac_000056.jsp&mid=WC0b01ac05805c516f |date=20180801232541 }}</ref><ref name="被禁1">{{cite web | title=Gadolinium-containing contrast agents: removal of Omniscan and iv Magnevist, restrictions to the use of other linear agents | website=GOV.UK | date=14 December 2017 | url=https://www.gov.uk/drug-safety-update/gadolinium-containing-contrast-agents-removal-of-omniscan-and-iv-magnevist-restrictions-to-the-use-of-other-linear-agents | access-date=29 August 2021 | archive-date=2020-11-09 | archive-url=https://web.archive.org/web/20201109011621/https://www.gov.uk/drug-safety-update/gadolinium-containing-contrast-agents-removal-of-omniscan-and-iv-magnevist-restrictions-to-the-use-of-other-linear-agents | dead-url=no }}</ref><ref name="被禁2">{{Cite web|title=EU pulls gadolinium contrast agents over deposition concerns|url=https://www.radiologybusiness.com/topics/policy/eu-pulls-gadolinium-contrast-agents-over-deposition-concerns|access-date=18 August 2020|website=www.radiologybusiness.com|archive-date=2018-01-23|archive-url=https://web.archive.org/web/20180123201546/http://www.radiologybusiness.com/topics/policy/eu-pulls-gadolinium-contrast-agents-over-deposition-concerns|dead-url=no}}</ref>

==结构性质==
钆喷酸属线性螯合物，其动力学络合稳定常数<math>lg K</math>=22.46<ref name = "Ga综述">{{cite journal |author1=P Caravan, JJ Ellison, TJ McMurry, RB Lauffer |title=Gadolinium (III) chelates as MRI contrast agents: structure, dynamics, and applications |journal=Chemical Reviews |date=1999 |volume=99 |pages=2293−2352 |doi=10.1021/cr980440x}}</ref>。

钆喷酸中心离子Ga<sup>3+</sup>配位数为9，螯合配体二乙三胺五乙酸拥有3个氮原子和五个[[羧基]]氧配齿与Ga<sup>3+</sup>螯合，剩余的Ga<sup>3+</sup>配位数与水分子氧进行配位<ref>{{cite journal |author1=Sherry AD, Caravan P, Lenkinski RE |title=Primer on gadolinium chemistry |journal=Journal of Magnetic Resonance Imaging |date=2009 |volume=30 |issue=6 |pages=1240–1248 |doi=10.1002/jmri.21966 |pmid=19938036}}</ref>。螯合配体与Ga<sup>3+</sup>形成变形三帽三棱柱几何结构,Ga-O<sub>水</sub>[[键长]]略长于Ga-O<sub>羧基</sub>，Ga-N<sub>中心</sub>键长略短于Ga-N<sub>两侧</sub></sub>。不同阳离子的钆喷酸盐咬角介于理想[[四角反棱柱形分子构型|四角反棱柱]]和理想{{le|三帽三棱柱|Tricapped trigonal prismatic molecular geometry}}之间<ref name = "Ga综述"/>。

Ga<sup>3+</sup>外层[[电子轨道]]含有7对自旋平行的未成对电子，<sup>8</sup>S电子基态使得Ga<sup>3+</sup>具有强[[顺磁性]]。水分子与顺磁性的Ga<sup>3+</sup>可逆结合在氢核磁共振中产生内界弛豫，影响T<sub>1</sub>和T<sub>2</sub>弛豫时间，造成MRI像衬度。<ref>{{cite journal | vauthors = Caravan P, Ellison JJ, McMurry TJ, Lauffer RB | title = Gadolinium(III) Chelates as MRI Contrast Agents: Structure, Dynamics, and Applications | journal = Chemical Reviews | volume = 99 | issue = 9 | pages = 2293–2352 | date = September 1999 | pmid = 11749483 | doi = 10.1021/cr980440x }}</ref>

==MRI造影剂==
=== 原理 ===
钆喷酸为离子型钆基造影剂，高络合稳定常数使得在体内很稳定，脱螯出有毒的Ga<sup>3+</sup>可忽略不计<ref>{{cite journal | title=Gadolinium-Based MRI Contrast Agents Induce Mitochondrial Toxicity and Cell Death in Human Neurons, and Toxicity Increases With Reduced Kinetic Stability of the Agent | vauthors=Bower DV, Richter JK, von Tengg-Kobligk H, Heverhagen JT, Runge VM | volume=54 | journal=Investigative Radiology | number=8 | date=August 2019 | pmid=31265439 | doi=10.1097/RLI.0000000000000567 | pages=453–463 | s2cid=164486744 | url=https://boris.unibe.ch/132314/ | access-date=2024-06-27 | archive-date=2024-12-13 | archive-url=https://web.archive.org/web/20241213142033/https://boris.unibe.ch/132314/ | dead-url=no }}</ref><ref>{{cite journal |author1=Alexander Radbruch , Lukas D. Weberling, Pascal J. Kieslich, Oliver Eidel, Sina Burth, Philipp Kickingereder, Sabine Heiland, Wolfgang Wick, Heinz-Peter Schlemmer, Martin Bendszus |title=Gadolinium Retention in the Dentate Nucleus and Globus Pallidus Is Dependent on the Class of Contrast Agent |journal=RADIOLOG |date=2015 |volume=275 |issue=3 |pages=783-791 |doi=10.1148/radiol.2015150337}}</ref>。
Ga<sup>3+</sup>的强顺磁性使得钆喷酸为阳性显影剂。Gd<sup>3+</sup>配位数为9，然而配体DTPA配位数为8，因此剩余的位点与水分子可逆结合在氢[[核磁共振]]中产生内界弛豫，减小和自旋-晶格弛豫时间T<sub>1</sub>和自旋-自旋弛豫时间T<sub>2</sub>，但T<sub>1</sub>弛豫时间减小占比更优(T<sub>1</sub>弛豫效率=4 mM<sup>-1</sup>s<sup>-1</sup>；T<sub>2</sub>弛豫效率=6 mM<sup>-1</sup>s<sup>-1</sup>)，使得T<sub>1</sub>加权图像更亮，形成对比度<ref name= "造影剂书"/>。
=== 作用 ===
静脉注射后，钆喷酸迅速扩散到血液和细胞外空间，其分布无器官专一性，与各组织供血和毛细血管通透性有关。分布半衰期12分钟，清除半衰期100分钟，药物原体经肾从尿液排出，少部分会分泌到胃肠道经粪便排出<ref name= "造影剂书"/>。作为一种高极性且相对较大的分子，钆喷酸在静脉注射后无法穿过脑部、睾丸、眼部等有毛细血管屏障的器官，因此其无法正常透过健康人体的血脑屏障，若血管异常或有血脑屏障异常的颅内病变（如[[胶质母细胞瘤]]），钆喷酸则会在病变部位透过血脑屏障，MRI图像上相应部分产生高亮。因此钆喷酸可用于识别血管病变和脑部肿瘤<ref>H. Scholz, G. Kuschinsky, R. H. Böger: ''Taschenbuch der Arzneibehandlung.'' Springer, 2005, S. 606. ({{Google Buch |BuchID=ZtgcBaofx5UC |Seite=606}})</ref>。

钆喷酸葡胺注射到关节中可进行延迟钆增强磁共振软骨成像（{{le|dGEMRIC|Delayed gadolinium-enhanced magnetic resonance imaging of cartilage}}），因钆喷酸葡胺独特的电子结构可实现逆向测量自旋-晶格弛豫时间T<sub>1</sub>，这是因为T<sub>1</sub>与[[软骨]]中[[蛋白聚糖]]聚集体浓度以及[[糖胺聚糖]]带电侧基有关<ref>{{cite journal | vauthors = Bashir A, Gray ML, Boutin RD, Burstein D | title = Glycosaminoglycan in articular cartilage: in vivo assessment with delayed Gd(DTPA)(2-)-enhanced MR imaging | url = https://archive.org/details/sim_radiology_1997-11_205_2/page/551 | journal = Radiology | volume = 205 | issue = 2 | pages = 551–558 | date = November 1997 | pmid = 9356644 | doi = 10.1148/radiology.205.2.9356644 }}</ref><ref>{{cite journal | vauthors = Bashir A, Gray ML, Hartke J, Burstein D | title = Nondestructive imaging of human cartilage glycosaminoglycan concentration by MRI | journal = Magnetic Resonance in Medicine | volume = 41 | issue = 5 | pages = 857–865 | date = May 1999 | pmid = 10332865 | doi = 10.1002/(sici)1522-2594(199905)41:5<857::aid-mrm1>3.0.co;2-e | s2cid = 22939233 | doi-access = free }}</ref>。
:[[File:Magnevist Bottle.JPG|150px|thumb|马根维显注射液]]

=== 风险 ===
作为含钆制剂，患有严重肾脏疾病以及肾功能不全的患者使用钆喷酸会引起[[肾源性系统性纤维化]]，因此该类人群被限制使用钆喷酸以及相关含钆显影剂。<ref name="murphy">{{cite journal | vauthors = Murphy KJ, Brunberg JA, Cohan RH | title = Adverse reactions to gadolinium contrast media: a review of 36 cases | url = https://archive.org/details/sim_ajr-american-journal-of-roentgenology_1996-10_167_4/page/847 | journal = AJR. American Journal of Roentgenology | volume = 167 | issue = 4 | pages = 847–849 | date = October 1996 | pmid = 8819369 | doi = 10.2214/ajr.167.4.8819369 | doi-access = free }}</ref><ref name="thomsen">{{cite journal | vauthors = Thomsen HS, Morcos SK, Dawson P | title = Is there a causal relation between the administration of gadolinium based contrast media and the development of nephrogenic systemic fibrosis (NSF)? | journal = Clinical Radiology | volume = 61 | issue = 11 | pages = 905–906 | date = November 2006 | pmid = 17018301 | doi = 10.1016/j.crad.2006.09.003 }}</ref>。长期使用会造成钆脑部沉积<ref name="被禁1"/><ref name="被禁2"/>。同时其不良发生率很低，但有既往有含碘显影剂以及含钆显影剂相关过敏史、以及含有基础疾病的使用者发生不良反应风险会增加<ref>{{cite journal |author1=周庆春 |title=189例磁共振对比剂钆喷酸普胺致不良反应病例的文献分析 |journal=抗感染药学 |date=2016 |volume=13 |issue=1 |pages=118-120 |doi=10.13493/j.issn.1672-7878.2016.01-041}}</ref><ref name="murphy"/>。
 


[[File:Sella mri-contra.jpg|250px|thumb|马根维显（10ml）作为脑垂体造影剂的MRI图像]]

==参考文献==
{{reflist}}

{{Contrast media |state=collapsed}}
[[Category:造影剂]]
[[category:钆化合物]]