摘要
Abstract
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.关键词
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Key words
Thyroid cancer/Nuclear medicine/Radioiodine refractory differentiated thyroid cancer/Molecular imaging/Radioligand therapy分类
医药卫生
