de Geus-Oei Lioe-Fee, Mavinkurve-Groothuis Annelies M C, Bellersen Louise, Gotthardt Martin, Oyen Wim J G, Kapusta Livia, van Laarhoven Hanneke W M
Department of Nuclear Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
J Nucl Med Technol. 2013 Sep;41(3):170-81. doi: 10.2967/jnumed.110.082784. Epub 2013 Aug 8.
New antitumor agents have resulted in significant survival benefits for cancer patients. However, several agents may have serious cardiovascular side effects. Left ventricular ejection fraction measurement by (99m)Tc multigated radionuclide angiography is regarded as the gold standard to measure cardiotoxicity in adult patients. It identifies left ventricular dysfunction with high reproducibility and low interobserver variability. A decrease in left ventricular ejection fraction, however, is a relatively late manifestation of myocardial damage. Nuclear cardiologic techniques that visualize pathophysiologic processes at the tissue level could detect myocardial injury at an earlier stage. These techniques may give the opportunity for timely intervention to prevent further damage and could provide insights into the mechanisms and pathophysiology of cardiotoxicity caused by anticancer agents. This review provides an overview of past, current, and promising newly developed radiopharmaceuticals and describes the role and recent advances of scintigraphic techniques to measure cardiotoxicity. Both first-order functional imaging techniques (visualizing mechanical [pump] function), such as (99m)Tc multigated radionuclide angiography and (99m)Tc gated blood-pool SPECT, and third-order functional imaging techniques (visualizing pathophysiologic and neurophysiologic processes at the tissue level) are discussed. Third-order functional imaging techniques comprise (123)I-metaiodobenzylguanidine scintigraphy, which images the efferent sympathetic nervous innervations; sympathetic neuronal PET, with its wide range of tracers; (111)In-antimyosin, which is a specific marker for myocardial cell injury and necrosis; (99m)Tc-annexin V scintigraphy, which visualizes apoptosis and cell death; fatty-acid-use scintigraphy, which visualizes the storage of free fatty acids in the lipid pool of the cytosol (which can be impaired by cardiotoxic agents); and (111)In-trastuzumab imaging, to study trastuzumab targeting to the myocardium. To define the prognostic importance and clinical value of each of these functional imaging techniques, prospective clinical trials are warranted.
新型抗肿瘤药物已给癌症患者带来显著的生存获益。然而，一些药物可能会有严重的心血管副作用。通过（99m）锝多门控放射性核素血管造影术测量左心室射血分数被视为测量成年患者心脏毒性的金标准。它能以高重现性和低观察者间变异性识别左心室功能障碍。然而，左心室射血分数降低是心肌损伤相对较晚的表现。能在组织水平可视化病理生理过程的核心脏病学技术可在更早阶段检测到心肌损伤。这些技术可能为及时干预以防止进一步损伤提供机会，并能深入了解抗癌药物所致心脏毒性的机制和病理生理学。本综述概述了过去、当前以及有前景的新开发放射性药物，并描述了闪烁成像技术在测量心脏毒性方面的作用和最新进展。文中讨论了一阶功能成像技术（可视化机械[泵]功能），如（99m）锝多门控放射性核素血管造影术和（99m）锝门控心血池单光子发射计算机断层显像，以及三阶功能成像技术（在组织水平可视化病理生理和神经生理过程）。三阶功能成像技术包括（123）I - 间碘苄胍闪烁显像，可对传出交感神经支配进行成像；具有多种示踪剂的交感神经元正电子发射断层显像；（111）铟 - 抗肌凝蛋白，它是心肌细胞损伤和坏死的特异性标志物；（99m）锝 - 膜联蛋白V闪烁显像，可可视化细胞凋亡和细胞死亡；脂肪酸利用闪烁显像，可可视化游离脂肪酸在细胞质脂质池中的储存情况（这可能会受到心脏毒性药物的损害）；以及（111）铟 - 曲妥珠单抗成像，用于研究曲妥珠单抗对心肌的靶向作用。为明确这些功能成像技术各自的预后重要性和临床价值，有必要开展前瞻性临床试验。
