心血管疾病PET显像剂研究进展

doi:10.7538/tws.2017.youxian.025

摘要/Abstract

摘要：

正电子发射断层（PET）显像可用于监测非侵袭性心血管病变，有良好的临床应用前景。各种显像剂的转化应用使PET从分子水平上早期发现和评估心血管疾病，提高了心血管疾病早期诊断和疗效监测的灵敏度和特异性。本文介绍了用于心血管疾病的PET显像剂及其应用进展。

关键词: 心血管疾病, 正电子发射断层（PET）, 放射性示踪剂

Abstract:

Positron emission tomography ( PET) imaging has successfully allowed the noninvasive detection of cardiovascular disease and shows good clinical application prospects. Development and translation application of various imaging agents furtherly enable PET imaging to be used for early detection and progression evaluation of cardiovascular diseases at molecular level, which can improve sensitivity and specificity of early diagnosis and monitoring of the diseases. This review mainly describes development and application progression of PET tracers for cardiovascular diseases imaging.

Key words: cardiovascular diseases, positron emission tomography, radioactive tracers

马慧;梁宏;徐万帮;唐刚华. 心血管疾病PET显像剂研究进展[J]. 同位素, 2018, 31(2): 114-122.

MA Hui;LIANG Hong;XU Wan-bang;TANG Gang-hua. Progress of PET Imaging Agents for Cardiovascular Diseases[J]. Journal of Isotopes, 2018, 31(2): 114-122.

参考文献

［1］Ametamey S M, Honer M, Schubiger P A. Molecular imaging with PET［J］. Chem Rev, 2008, 108(5): 1501-1516.
［2］Small G R, Wells R G, Schindler T, et al. Advances in cardiac SPECT and PET imaging: overcoming the challenges to reduce radiation exposure and improve accuracy［J］. Can J Cardiol, 2013, 29(3): 275-284.
［3］唐刚华. PET药物及其研究现状与进展［J］. 国际放射医学核医学杂志,1999,23(5):193-197.Tang Ganghua. Research and development of PET agents［J］. Journal of Isotopes ,1999, 23(5): 193-197(in Chinese).
［4］Sogbein O O, Galarneau M P, Schindler T H, et al. New SPECT and PET radiopharmaceuticals for imaging cardiovascular disease［J］. BioMed Res Int, 2014, 2014(8): 1-24.
［5］谢博洽. 正电子心肌灌注显像剂的临床应用及研究进展［J］. 同位素,2009,22(4):230-236.Xie Boqia. Research progress and clinical applicationof cardiac positron emission tomography perfusion tracers［J］. Journal of Isotopes, 2009, 22(4): 230-236(in Chinese).
［6］Li Y, Zhang W, Wu H, et al. Advanced tracers in PET imaging of cardiovascular disease［J］. Biomed Res Int, 2014, 2014: 504-532.
［7］Ji A Y, Jin Q M, Zhang D J, et al. Novel ¹⁸F-lbeled 1-hydroxyanthraquinone derivatives for necrotic myocardium imaging［J］. ACS Med Chem Lett, 2016, 8(2): 191-195.
［8］Madar I, Ravert H T, Du Y, et al. Characterization of uptake of the new PET imaging compound ¹⁸F-fluorobenzyl triphenyl phosphonium in dog myocardium［J］. J Nucl Med, 2006, 47(8): 1359-1366.
［9］Shoup T M, Elmaleh D R, Brownell A L, et al. Evaluation of (4-［¹⁸F］-Fluorophenyl) triphenylphosphonimion. A potential myocardial blood flow agent for PET［J］. Mol Imaging Biol, 2011, 13(3): 511-517.
［10］Aydinbelge F N, Sadic M, Korkmaz M. Current status of myocardial perfusion imaging radiopharmaceuticals for SPECT and PET imaging modalities［J］. Int J Res Med Sci, 2016, 5(1): 1-7.
［11］Yang B Y, Jeong J M, Kim Y J,et al. Formulation of ⁶⁸Ga-BAPEN kit for myocard-ial positron emission tomography imaging and biodistribution study［J］. Nucl Med Biol, 2010, 37(2):149-155.
［12］Thackeray J T, Bankstahl J P, Yong W, et al. Targeting post-infarct inflammation by PET imaging: comparison of ⁶⁸Ga-citrate and ⁶⁸Ga-DOTATATE with ¹⁸F-FDG in a mouse model［J］. Eur J Nucl Med Mol Imaging, 2015, 42(2): 317-327.
［13］Wu S, Zhu Y, Liu H, et al. In vivo dynamic metabolic changes after transplantation of induced pluripotent stem cells for ischemic injury［J］. J Nucl Med & Mol Imaging, 2016, 57(12): 2012-2015.
［14］Derlin T, Habermann C R, Lengyel Z, et al. Feasibility of ¹¹C-acetate PET/CT for imaging of fatty acid synthesis in the atherosclerotic vessel wall［J］. J Nucl Med, 2011, 52(12): 1848-1854.
［15］Thackeray J T, Bankstahl J P, Wang Y,et al. Targeting amino acid metabolism for molecular imaging of inflammation early after myocardial infarction［J］. Theranostics, 2016, 6(11):1768-1779. 
［16］Matter C M, Wyss M T, Meier P, et al. ¹⁸F-choline images murine atherosclerotic plaques ex vivo［J］. Arterioscler Thromb Vasc Biol, 2006, 26(3): 584-589.
［17］Laitinen I E, Luoto P, Nagren K, et al. Uptake of ¹¹C-choline in mouse atherosclerotic plaques［J］. JNucl Med, 2010, 51(5): 798-802.
［18］Joshi N V, Vesey A T, Williams M C, et al. ¹⁸F-fluoride positron emission tomography for identify cation of ruptured and high-risk coronary atherosclerotic plaques: a prospective clinical trial［J］. Lancet, 2014, 383(9918): 705-713.
［19］张弘,蒋宁一. 心肌乏氧显像及其临床应用［J］. 国际放射医学核医学杂志,2004,28(3):113-117.Zhang Hong, Jiang Ningyi.Myocardial hypoxia imaging and clinical application［J］. Foreign Med Sci. Sec Radiat Med Nucl Med, 2004, 28(3): 113-117(in Chinese).
［20］Mateo J, Izquierdo-Garcia D, Badimon J J, et al. Noninvasive assessment of hypoxia in rabbit advan-ced atherosclerosis using ¹⁸F-fluoromisonidazole positron emission tomographic imaging［J］. Circ Car-diovasc Imaging, 2014, 7(2): 312-320.
［21］ Zhang T, Das S K, Fels D R, et al. PET with ⁶²Cu ATSM and ⁶²Cu PTSM is a useful imaging tool for hypoxia and perfusion in pulmonary lesions［J］. AJR Am J Roentgenol, 2013, 201(5): 698-706.
［22］Sharma S K. Pet radiopharmaceuticals for personalized medicine［J］. Curr Drug Targets, 2016, 17(999): 1894-1907.
［23］Hu S, Kiesewetter D O, Zhu L, et al. Longitudinal PET imaging of doxorubicin induced cell death with ¹⁸F-annexin V［J］. Mol Imaging Biol, 2012, 14(6): 762-770.
［24］Zhao M, Zhu X, Ji S, et al. ^99mTc-Labeled C2A domain of synaptotagmin I as a target-specific Mo-lecular probe for noninvasive imaging of acute myocardial infarction［J］. J Nucl Med, 2006, 47(8): 1367-1374.
［25］Schellenberger E A, Reynolds F, Weissleder R, et al. Surface-functionalized nanoparticle library yields probes for apoptotic cells［J］. Chembiochem, 2004, 5(3): 275-279.
［26］Madar I, Huang Y, Ravert H,et al. Detection and quantification of the evolution dynamics of apoptosis using the PET voltage sensor ¹⁸F fluorobenzyl triphenyl phosphonium［J］. J Nucl Med, 2009,50(5): 774-780.
［27］Höglund J, Shirvan A, Antoni G, et al. ¹⁸F-ML-10, a PET tracer for apoptosis: first human study［J］. J Nucl Med, 2011, 52(5): 720-725.
［28］付占立,王荣福. 心脏神经显像［J］. 中华核医学与分子影杂志,2005,25(5):314-317.Fu ZhanLi ,Wang RongFu. Cardiac neurological imaging［J］ . Chin J Nucl Med, 2005, 25(5): 314-317(in Chinese).
［29］Zhang H, Huang R, Pillarsetty N V, et al. Synthesis and evaluation of ［¹⁸F］-Fluorine-labeled benzyl-guanidine analogs for targeting the human norepinephrine transporter［J］. Eur J Nucl Med Mol Imaging, 2014, 41(2): 322.
［30］Li S T, Holmes C, Kopin I J, et al. Aging-related changes in cardiac sympathetic function in humans, assessed by 6-¹⁸F-fluorodopamine PET scanning［J］. J Nuc Med, 2003, 44(10): 1599-1603. 
［31］Jung Y W, Jang K S, Gu G, et al. ［¹⁸F］Fluoro-Hydroxyphenethylguanidines: efficient synthesis and comparison of two structural isomers as radiotracers of cardiac sympathetic innervation［J］. ACS Chem Neurosci, 2017, Mar 27. ［Epub ahead of print］ doi: 10.1021/acschemneuro.7b00051.
［32］Gaertner F C, Wiedemann T, Yousefi B H, et al. Preclinical evaluation of ¹⁸F-LMI1195 for in vivo imaging of pheochromocytoma in the MENX tumor model［J］. J Nucl Med,2013, 54(12): 2111.
［33］Park-Holohan S J, Asselin M C, Turton D R, et al. Quantification of ［¹¹C］GB67 binding to cardiacalphal-adrenoceptors with positron emission tomography: validation in pigs［J］. Eur J Nucl Med Mol Imaging, 2008, 35(9): 1624-1635.
［34］Hendrikx G, Vöö S, Bauwens M, et al. SPECT and PET imaging of angiogenesis andarteriogenesis in preclinical models of myocardialischemia and peripheral-vascular disease［J］. Eur J Nucl Med Mol Imaging, 2016, 43(13): 2433-2447.
［35］Makowski M R, Ebersberger U, Nekolla S, et al. In vivo molecular imaging of angiogenesis, targeting alphavbeta3 integrin expression, in a patient after acute myocardial infarction［J］. Eur Hear J, 2008, 29(18): 2201.
［36］Van Der Gucht A, Galat A, Rosso J, et al. ¹⁸F-NaF PET/CT imaging in cardiac amyloidosis［J］. J Nucl Cardiol, 2016, 23(4): 846-849.
［37］Lee S P, Lee E S, Choi H, et al. ¹¹C-Pittsburgh B PET imaging in cardiac amyloidosis［J］. JACC Car-diovasc Imaging, 2015, 8(1): 50-59.
［38］Sarikaya I. Cardiac applications of PET［J］. Nucl Med Commun, 2015, 36(10): 971-985.
［39］Lohrke J, Siebeneicher H, Berger M, et al. ¹⁸F-GP1, a novel fluorine-18 labeled tracer designed for PET imaging of thrombi with high detection sensitivity and low background［J］. J Nucl Med & Mol Imaging, 2017, Mar 16. ［Epub ahead of print］. doi: 10.2967/jnumed.116.188896.
［40］Garcia J, Tang T, Louie A Y. Nanoparticle-based multimodal PET/MRI probes［J］. Nanomedicine, 2015, 10(8): 1343-1359.
［41］Tu C, Ng T S, Jacobs R E, et al. Multimodality PET/MRI agents targeted to activated macrophages［J］. Journal of Biological Inorganic Chemistry, 2014, 19(2): 247-258.
［42］刘志弢,袁绍华. PET/MRI在心脏核医学中的应用研究［J］. 核电子学与探测技术, 2013,33(3):263-271.Liu Zhitao,Yuan Shaohua. Analysis on the application trends of PET/MＲI in nuclear cardiology［J］. Nuclear Electronics & Detection Technology, 2013, 33(3): 263-271(in Chinese).
［43］Torigian D A, Zaidi H, Kwee T C, et al. PET/MR imaging: technical aspects and potential clinical applications［J］. Radiology, 2013, 267(1): 26-44.

[1]	余凯翔;杨征敏;周兵;徐凌锋;李书琰;陈沪飞;王伟. 放射性同位素碳-14标记毒死蜱的合成与分析[J]. 同位素, 2020, 33(6): 409-416.
[2]	唐萌;吴文凯. 肿瘤血管内皮生长因子受体PET示踪剂研究进展[J]. 同位素, 2007, 20(3): 178-185.
[3]	作者. 胆碱代谢PET显像的临床应用[J]. 同位素, 2004, 17 (1 ): 53-53 .
[4]	作者. 胆碱代谢PET显像的临床应用[J]. 同位素, 2004, 17 (1 ): 53-53 .
[5]	作者. 直埋电缆示踪~(85)Kr法探漏研究 [J]. 同位素, 1990, 3 (1 ): 11-11 .
[6]	作者. 天然放射性示踪剂的应用——Ⅴ.用~(210)Pb示踪研究九龙江泥沙对厦门航道的影响 [J]. 同位素, 1989, 2 (4 ): 211-211 .