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肿瘤是导致中国人群死亡的首要原因[1]。2020年,全球24%的新发恶性肿瘤患者和30%的恶性肿瘤死亡患者来自中国[2]。随着现代医学和肿瘤治疗技术的不断发展,越来越多的肿瘤患者的生存期得到延长,然而肿瘤患者合并心血管疾病的概率却在不断升高[3]。研究结果显示,相较于不合并心血管疾病的肿瘤患者,合并心血管疾病的患者的全因死亡风险增高3.78倍,并且在长期生存的肿瘤患者中,有8.8%的患者死于心血管疾病[4]。这可能影响肿瘤患者的短期及长期临床获益[5]。基于此,肿瘤心脏病学作为针对肿瘤患者心血管疾病的诊断、防治及预后问题研究的一个领域,正在逐渐兴起并发展[6]。
近年来,核医学在各类疾病诊疗中发挥的作用越来越受到人们的关注,核医学显像在肿瘤治疗引发的心脏毒性的早期诊断、监测及评估方面占据重要地位[7]。虽然心脏MRI以及经胸壁心脏超声(transthoracic echocardiography,TTE)的出现为临床提供了更多的选择,但核医学显像仍然在肿瘤治疗引发的心脏毒性的评估和管理中具有一定的临床价值。
本文将对目前核医学显像在肿瘤心脏病学中的研究进展进行综述,为肿瘤治疗引发的心脏毒性的评估和管理提供核医学层面的指导和总结。
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有研究者发现,许多能够靶向心脏毒性早期标志物(如交感神经末梢、血管生成、活性氧和细胞凋亡)的显像剂,可以作为除18F-FDG外,为肿瘤治疗引发的心脏毒性的诊断及预后评估提供帮助的新型分子显像剂[9]。111In-抗肌球蛋白抗体可以在心肌细胞坏死时与暴露的心肌肌球蛋白结合[40],相关研究结果显示,应用阿霉素治疗后LVEF降低≥5%的患者,其心肌对111In-抗肌球蛋白抗体有较高的摄取,而未用药且未出现心肌病的患者的显像结果为阴性[40]。123I-间碘苄胍是心肌交感神经摄取的一种肾上腺素类似物,因此能够进行心肌交感神经显像。虽已有研究结果证实123I-间碘苄胍显像可以反映应用蒽环类和曲妥珠单抗治疗对乳腺癌患者心脏损伤的影响[41],且可以成功预测心衰患者不良结局的风险[42],但对于123I-间碘苄胍显像的诊断效能仍存在争议[43]。99Tcm-膜联蛋白V 是一种与细胞凋亡相关的分子,动物实验结果显示,阿霉素的使用剂量与心肌对99Tcm-膜联蛋白V 的摄取呈正相关[44],但仍缺乏相关的临床研究结果支持。18F-二氢乙锭是一类反映活性氧水平的标志物,有研究结果显示,在接受蒽环类药物治疗后4周的大鼠模型中,18F-二氢乙锭可以显示其心脏超氧化物含量的增加,而TTE则是在治疗后6周才检测到LVEF的下降[45],该结果提示18F-二氢乙锭相较于TTE可以更早地发现心脏毒性的发生。
综上,不同分子显像技术在肿瘤治疗引发的心脏毒性中的研究逐渐受到人们的关注(表1),但由于临床研究相对较少,分子显像技术的临床价值有待商榷。现有研究结果提示分子显像技术仍有潜力成为肿瘤治疗引发的心脏毒性研究的重要工具,需要对潜在显像剂和分子显像技术进行更全面且深入的开发和研究。
显像剂 靶点或摄取机制 心血管显像应用 显像方式 99Tcm-MIBI 线粒体 心肌灌注 SPECT 99Tcm-膜联蛋白V 磷脂酰丝氨酸 细胞凋亡 SPECT 99Tcm-替曲膦 线粒体 心肌灌注 SPECT 111In-抗肌球蛋白抗体 肌球蛋白 细胞坏死 SPECT 111In-曲妥珠单抗 人类表皮生长
因子受体2细胞凋亡 SPECT 123I-间碘苄胍 去甲肾上腺素
转运蛋白交感神经完
整性SPECT 201TlCl Na+/K+-ATP酶 心肌灌注 SPECT 13NH3 谷氨酰胺合成酶 心肌灌注 PET H215O 间质或细胞内 心肌灌注 PET 18F-Mitophos 线粒体 心肌灌注 PET 82RbCl Na+/K+-ATP酶 心肌灌注 PET 11C-羟基麻黄碱 去甲肾上腺素
转运蛋白交感神经完
整性PET 11C-乙酸盐 克雷伯氏循环 氧化代谢 PET 18F-FDG 葡萄糖转运体 葡萄糖代谢 PET 18F-二氢乙锭 活性氧 细胞毒性 PET 注:MIBI为甲氧基异丁基异腈;FDG为氟脱氧葡萄糖;SPECT为单光子发射计算机体层摄影术;PET为正电子发射断层显像术 表 1 肿瘤治疗引发的心脏毒性相关的放射性显像剂概览
Table 1. Overview of radioactive imaging agents related to cardiotoxicity caused by tumor treatment
核医学显像在肿瘤心脏病学中的研究进展
Research progress of nuclear medicine imaging in cardio-oncology
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摘要: 近年来,肿瘤心脏病学成为识别、预防和治疗肿瘤本身及肿瘤治疗引发的心血管并发症的一个新兴领域,并随着患者例数的增加逐渐受到人们的关注。核医学显像在肿瘤心脏病学的研究中发挥了重要作用,其可以帮助早期准确地诊断及监测肿瘤治疗引发的心脏毒性,有效改善肿瘤患者的预后。基于此,笔者对核医学显像在肿瘤心脏病学中的研究进展进行综述。Abstract: In recent years, cardio-oncology has become a new field to identify, prevent and treat the cardiovascular complications caused by tumor itself or tumor treatment. With the increase in the number of patients, it has gradually attracted people's attention. Nuclear medical imaging plays an important role in the research of cardio-oncology, which can help to early and accurately diagnose and monitor the cardiotoxicity caused by tumor treatment, and effectively improve the prognosis of tumor patients. Based on this, the author reviewed the research progress of nuclear medicine imaging in cardio-oncology.
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Key words:
- Nuclear medicine /
- Radionuclide imaging /
- Cardiotoxicity /
- Cardio-oncology
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表 1 肿瘤治疗引发的心脏毒性相关的放射性显像剂概览
Table 1. Overview of radioactive imaging agents related to cardiotoxicity caused by tumor treatment
显像剂 靶点或摄取机制 心血管显像应用 显像方式 99Tcm-MIBI 线粒体 心肌灌注 SPECT 99Tcm-膜联蛋白V 磷脂酰丝氨酸 细胞凋亡 SPECT 99Tcm-替曲膦 线粒体 心肌灌注 SPECT 111In-抗肌球蛋白抗体 肌球蛋白 细胞坏死 SPECT 111In-曲妥珠单抗 人类表皮生长
因子受体2细胞凋亡 SPECT 123I-间碘苄胍 去甲肾上腺素
转运蛋白交感神经完
整性SPECT 201TlCl Na+/K+-ATP酶 心肌灌注 SPECT 13NH3 谷氨酰胺合成酶 心肌灌注 PET H215O 间质或细胞内 心肌灌注 PET 18F-Mitophos 线粒体 心肌灌注 PET 82RbCl Na+/K+-ATP酶 心肌灌注 PET 11C-羟基麻黄碱 去甲肾上腺素
转运蛋白交感神经完
整性PET 11C-乙酸盐 克雷伯氏循环 氧化代谢 PET 18F-FDG 葡萄糖转运体 葡萄糖代谢 PET 18F-二氢乙锭 活性氧 细胞毒性 PET 注:MIBI为甲氧基异丁基异腈;FDG为氟脱氧葡萄糖;SPECT为单光子发射计算机体层摄影术;PET为正电子发射断层显像术 -
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