2025年甲状腺癌核医学诊疗新进展OA
Advances in nuclear medicine diagnosis and treatment of thyroid cancer in 2025
甲状腺癌是内分泌系统最常见的恶性肿瘤,尽管多数分化型甲状腺癌(differentiated thyroid cancer,DTC)患者预后良好,但放射性碘难治性DTC(radioiodine refractory DTC,RAIR-DTC)、甲状腺未分化癌(anaplastic thyroid cancer,ATC)及甲状腺髓样癌(medullary thyroid cancer,MTC)的精准诊疗仍是临床面临的重大挑战.近年来核医学在甲状腺癌领域取得了显著进展,诊疗模式正经历从经验导向到个体化精准导向的深刻转型.在发病机制解析方面,研究视角已从单一的驱动基因突变延伸至肿瘤微环境(tumor microenvironment,TME)的空间动态演化及钠碘同向转运体(sodium-iodide symporter,NIS)的转运稳态控制.利用单细胞转录组与空间转录组技术,研究者系统绘制了甲状腺癌演进的空间图谱,识别出驱动恶性进展的关键基质组分及免疫调控节点.同时,针对NIS蛋白的研究揭示了除转录抑制外的多重功能屏障,由病理性内吞加速导致的细胞膜上NIS表达耗竭,以及微环境应激诱发的非编码RNA网络异常及染色质重塑,共同构成了从转录后蛋白稳态到表观遗传修饰的多重功能屏障.在分子影像诊断领域,新型多靶点探针的应用显著提升了复杂病灶的检出精度.针对 DTC,除了传统的131I 显像与18F-氟代脱氧葡萄糖(18F-fluorodeoxyglucose,18F-FDG)的应用评估外,针对成纤维细胞活化蛋白(fibroblast activation protein,FAP)、前列腺特异性膜抗原(prostate-specific membrane antigen,PSMA)及钠依赖性维生素C转运蛋白2(sodium-dependent vitamin C transporter 2,SVCT2)等靶点的新型靶向显像剂在探测微小转移灶、评估肿瘤异质性方面展现出良好的应用价值.针对MTC,18F-DOPA仍是生化复发评估的首选,但近期研究证实FAP抑制剂(FAP inhibitor,FAPI)显像及胆囊收缩素-2受体(cholecystokinin-2 receptor,CCK-2R)靶向探针(如68Ga-DOTA-MGS5)在识别微小病灶及评估侵袭性方面具有重要补充作用.在核医学治疗方面,诊疗一体化路径取得了实质性突破.针对RAIR-DTC,基于丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)信号转导通路抑制剂的短程再分化策略已进入临床转化阶段,meta分析证实其诱导摄碘恢复的成功率达50%,且安全性良好.对于常规治疗耐药的患者,放射性配体治疗展现出一定的应用前景,177Lu-EB-FAPI及177Lu-PSMA等药物在提升肿瘤靶向蓄积及延长患者生存期方面获得了初步循证医学证据的支持.α核素211At-NaAt首次人体试验提供了临床安全性、器官辐射剂量学和疗效数据.综上,甲状腺癌核医学的发展正立足于多维度的机制突破和技术革新,随着诊疗一体化策略的深度推广及新型核素药物的持续开发,核医学将在甲状腺癌的精准管理路径中发挥更为重要的作用.
Thyroid cancer is the most prevalent malignancy of the endocrine system.Although most differentiated thyroid cancers(DTC)carry a favorable prognosis,the precision diagnosis and management of radioiodine-refractory DTC(RAIR-DTC),anaplastic thyroid cancer(ATC)and medullary thyroid cancer(MTC)remain formidable clinical challenges.In recent years,nuclear medicine has achieved significant progress in the field of thyroid cancer,with the diagnostic and therapeutic paradigm undergoing a profound transformation from an empirical approach toward individualized precision medicine.Regarding basic mechanistic elucidation,research perspectives have expanded from single driver gene mutations to the spatial dynamic evolution of the tumor microenvironment(TME)and the transport homeostasis control of the sodium-iodide symporter(NIS).Utilizing single-cell and spatial transcriptomics,researchers have systematically mapped the spatial landscape of thyroid cancer evolution,identifying key stromal components and immune regulatory nodes that drive malignant progression.Concurrently,studies focusing on the NIS protein have revealed that the depletion of NIS expression on the plasma membrane driven by accelerated pathological endocytosis,along with the aberrant non-coding RNA networks and chromatin remodeling induced by microenvironmental stress,collectively constitute multiple functional barriers spanning from post-translational protein homeostasis to epigenetic modifications.In the domain of molecular imaging,the application of novel multi-target probes has significantly enhanced the detection precision of complex lesions.For DTC,beyond the evaluation of traditional 131I imaging and 18F-fluorodeoxyglucose(18F-FDG),novel targeted imaging agents such as fibroblast activation protein(FAP),prostate-specific membrane antigen(PSMA),and sodium-dependent vitamin C transporter 2(SVCT2)have demonstrated superior signal-to-noise ratios in detecting micro-metastases and assessing heterogeneity.For MTC,18F-DOPA remains the primary choice for biochemical recurrence assessment;however,recent studies confirm that FAP inhibitor(FAPI)and cholecystokinin-2 receptor(CCK-2R)-targeted probes(e.g.,68Ga-DOTA-MGS5)imaging provide critical supplementary value in identifying micro-lesions and evaluating aggressiveness.In the context of nuclear medicine therapy,the theranostic pathway has achieved substantive breakthroughs.For RAIR-DTC,short-course redifferentiation strategies based on mitogen-activated protein kinase(MAPK)signal transduction pathway inhibitors have entered the clinical translation phase,with meta-analyses confirming a 50%success rate in inducing the restoration of iodine uptake with a favorable safety profile.For patients resistant to conventional treatments,radioligand therapy shows promising prospects.Specifically,agents such as 177Lu-EB-FAPI and 177Lu-PSMA have received preliminary evidence-based support for enhancing tumor targeted accumulation and extending survival.The first-in-human trial of the α-emitting radionuclide 211At-NaAt provided data on clinical safety,organ radiation dosimetry and efficacy.In conclusion,the recent development of nuclear medicine in thyroid cancer is rooted in multi-dimensional mechanistic breakthroughs and technological innovations.With the widespread implementation of theranostic strategies and the continuous development of novel radiopharmaceuticals,nuclear medicine will play an increasingly vital role in the precision management of thyroid cancer.
张歆玥;黄蕤
四川大学华西医院核医学科,四川 成都 610041四川大学华西医院核医学科,四川 成都 610041
医药卫生
甲状腺癌核医学放射性碘难治性分化型甲状腺癌分子影像放射性配体治疗
Thyroid cancerNuclear medicineRadioiodine refractory differentiated thyroid cancerMolecular imagingRadioligand therapy
《中国癌症杂志》 2026 (7)
642-652,11
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