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淋巴瘤是最早发现的免疫系统恶性肿瘤之一,其发生主要与免疫应答过程中淋巴细胞增殖分化产生的免疫细胞的某种恶变有关,按组织病理学改变可分为霍奇金淋巴瘤(Hodgkin lymphoma,HL)和非霍奇金淋巴瘤(non-Hodgkin lymphoma,NHL)。18F-FDG通过示踪葡萄糖的摄取和磷酸化过程,可灵敏地显示机体中葡萄糖酵解水平较高的肿瘤组织,是目前临床上应用最广泛的代谢显像剂。18F-FDG PET/CT是目前临床使用最普遍的淋巴瘤显像技术,在淋巴瘤的诊疗决策,包括识别CT漏诊的肿瘤区域以实现准确分期、预测化疗患者的预后并确定可在巩固放疗中获益的患者中发挥着关键作用[1]。目前国际公认的淋巴瘤影像分期和疗效评价标准Lugano分类[2]强调了18F-FDG PET/CT显像的关键作用,推荐18F-FDG PET/CT作为所有18F-FDG摄取增高的淋巴瘤患者影像分期的“金标准”和NHL患者治疗中期和治疗结束后疗效评价的重要手段[3]。18F-FDG PET/CT显像在早期诊断淋巴瘤标准化疗导致的治疗相关心脏不良反应方面也具有一定的效能,可辅助临床医师调整治疗方案,尽量避免疾病进入心脏失代偿期[4]。
尽管18F-FDG PET/CT在淋巴瘤诊疗的各个阶段均发挥重要作用,但其也存在一些不足:(1)非恶性病变,如肉芽肿性炎症、化疗后淋巴样增生、脂肪坏死等均摄取18F-FDG,这可能导致肿瘤的分期产生误差或出现假阳性结果,影响18F-FDG PET/CT对淋巴瘤的预测价值;(2)18F-FDG PET/CT的诊断效能易受多种因素的干扰,如显像时患者的血糖水平、肿瘤的组织病理学亚型、实际的治疗方案等;(3)预测患者生存情况的肿瘤代谢体积(MTV)和病灶糖酵解总量(TLG),用于疗效评价的治疗前后SUVmax的下降值等重要的半定量分析参数缺乏标准化的检测规范与针对其效能的进一步的前瞻性试验的验证结果;(4)18F-FDG PET/CT对HL患者干细胞移植前后、中期治疗反应及预后等的评估效果较好,但对大部分NHL患者的评估效能缺乏充分的研究结果进行证明;(5)18F-FDG PET/CT在治疗后完全缓解的淋巴瘤患者的常规随访和疾病监测中没有明确的作用[1-2,5-8]。
PET/CT为淋巴瘤提供了一种动态的、个性化的诊疗手段,其面临的挑战在于如何更加精准地实现淋巴瘤的特异性靶向诊疗,即根据患者特点(年龄、健康状况、病程进展阶段、治疗反应)和肿瘤生物学特征(基因组、蛋白表达与分子表型、免疫微环境)制定更有针对性的诊疗策略。因此,越来越多的研究聚焦于非18F-FDG PET分子显像,研究人员探索通过非18F-FDG PET/CT或PET/MRI实现淋巴瘤靶向诊疗的优化方案。本文聚焦于其他生化代谢显像、放射免疫显像、受体显像等非18F-FDG PET分子显像技术在淋巴瘤中的显像特点和研究进展,探讨非18F-FDG显像剂的潜在应用价值,以期为淋巴瘤在核医学领域的基础研究和临床诊疗提供新的思路。
非18F-FDG PET分子显像在淋巴瘤中的应用进展
Application progress of non-18F-FDG PET molecular imaging in lymphoma
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摘要: 淋巴瘤是一种起源于淋巴结和淋巴组织的免疫系统恶性肿瘤,具有起病隐匿、侵袭性强等特点,是我国发病率增速最快的肿瘤之一。目前,18F-FDG PET/CT已经成为恶性淋巴瘤初始分期、再分期、早期治疗反应及疗效评估、预后预测与随访的重要影像技术。由于淋巴瘤的异质性,如侵袭性、组织来源、免疫表型、病程阶段、不同人群治疗反应等的差异,非18F-FDG PET显像技术在一些特定类型淋巴瘤的靶向诊疗中表现出较18F-FDG PET/CT更明显的优势。笔者聚焦于非18F-FDG PET分子显像在淋巴瘤中的研究进展,比较了非18F-FDG显像剂与传统显像剂18F-FDG在淋巴瘤诊疗过程中的异同、优势与不足、应用特色和发展潜能,期望为淋巴瘤特异性靶向诊疗和个性化精准医疗提供新的思路和方法。
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关键词:
- 淋巴瘤 /
- 氟脱氧葡萄糖F18 /
- 正电子发射断层显像术 /
- 分子显像 /
- 靶向诊疗
Abstract: Lymphoma is a malignant tumor of the immune system originating from lymph nodes and lymphoid tissues. It is characterized by insidious onset and strong invasion, and is one of the tumors with the fastest growing incidence rate in China. At present, PET/CT has been an important imaging technique for the initial staging, re-staging, early treatment response, efficacy evaluation, prognosis prediction, and follow-up of malignant lymphoma. Due to the heterogeneity of lymphoma, such as different types of lymphoma in invasiveness, tissue origins, immune phenotypes, the stage of disease, and treatment response of different populations, non-18F-FDG PET imaging technologies are expected to show advantages over 18F-FDG PET/CT in the targeted diagnosis and treatment of some specific types of lymphoma. We focused on the research progress of non-18F-FDG PET molecular imaging in lymphoma, comparing the similarities and differences, advantages and disadvantages, application characteristics and development potentials between non-18F-FDG imaging agents and traditional imaging agent 18F-FDG, so as to provide new ideas and methods for the specific targeted diagnosis and treatment and personalized precision medicine of lymphoma. -
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