PET tracers targeting pathophysiological mechanisms of ischemic stroke: A comprehensive review
缺血性卒中占全部卒中六成以上，从血管闭塞到功能障碍和认知衰退链条长、环节多。华中科技大学同济医学院附属同济医院核医学科朱小华、黄传志、杨婧菲据此病理链条，系统梳理近二十年PET示踪剂研究，用一张“PET路径图”将全过程拆解为七大环节，每环均有探针可看见、可量化。
Prof. Zhu Xiaohua’s team at Tongji Hospital presents a comprehensive roadmap of PET tracers for ischemic stroke.
第一环节聚焦动脉闭塞与血栓。[18F]NaF可识别粥样斑块微钙化，[18F]GP1与[68Ga]fucoidan能捕捉活化血小板，三者均已用于卒中风险分层与预后评估。
[18F]NaF identifies vulnerable plaques, while [18F]GP1 and [68Ga]fucoidan detect activated platelets, enabling risk stratification.
第二环节评估血流与缺氧。[15O]H₂O被公认为脑血流量化金标准，可验证MRI半暗带准确性；[18F]FMISO则在超急性期标记缺氧细胞，直接勾画出可挽救组织范围。
[15O]H₂O quantifies cerebral blood flow and validates MRI penumbra; [18F]FMISO maps hypoxia within the hyper-acute window.
第三环节解析代谢功能障碍。葡萄糖代谢方面，[18F]FDG在发病三天后显示梗死灶的灵敏度优于CT。从化学药、纳米颗粒到干细胞移植、神经调控，各类治疗开发过程中普遍采用[18F]FDG作为评价工具。此外，[11C]MET可反映氨基酸转运与蛋白合成，为神经功能评估提供独特视角。
[18F]FDG outperforms CT after day 3 and tracks metabolic recovery within 11 days in treated animals, serving as a universal efficacy readout for drugs, nanoparticles, stem cells, and neurostimulation. [11C]MET offers a distinct perspective on amino acid metabolism and neuroplasticity.
第四环节锁定神经炎症。TSPO探针[11C]PK11195、[18F]GE-180、[11C]DPA-713能“点亮”激活的小胶质细胞，为抗炎治疗用药时机和疗效评估提供“可视化标尺”。针对σ1R的[18F]FBFP则另辟蹊径，直接显示卒中后受体变化，信号与神经功能恢复及溶栓疗效相关，为神经保护机制研究打开新窗口。
TSPO ligands ([11C]PK11195, [18F]GE-180, [11C]DPA-713) visualize microglial activation; simplified protocols shorten scan time, and uptake reduction mirrors anti-inflammatory efficacy. The σ1R tracer [18F]FBFP reveals receptor alterations linked to functional recovery and thrombolysis outcome, opening a new window for neuroprotection research.
第五环节监测血管通透性。 [18F]BR-351显示基质酶活跃区域，提供神经炎症显像之外的新视角；[68Ga]ABY-028或[68Ga]AGuIX纳米颗粒则直接标记血浆外渗点，两者配合可算出屏障“缺口”大小，也便于随访药物修复效果。
[18F]BR-351 and albumin-based nanoparticles quantify blood–brain barrier leakage, providing complementary views beyond inflammation.
第六环节量化细胞死亡与突触损伤。[18F]FGA与[68Ga]TC3-OGDOTA只进死细胞，与凋亡酶共定位，梗死核心边缘锐利。SV2A探针[11C]UCB-J则把“断联”量化，发现病灶侧及对侧小脑同步减少，为远隔功能抑制提供直接证据。
[18F]FGA and [68Ga]TC3-OGDOTA selectively label necrotic tissue for core delineation, while the SV2A tracer [11C]UCB-J reveals remote synaptic loss.
第七环节追踪异常蛋白沉积。Aβ探针[11C]PiB、[18F]Florbetapir和tau探针[18F]MK-6240在卒中后数月仍可见摄取增高，提示病灶周围可能出现继发蛋白病变，与认知下降时间线吻合。
Aβ ([11C]PiB, [18F]Florbetapir) and tau ([18F]MK-6240) probes show sustained uptake months after stroke, linking secondary proteinopathy to cognitive decline.
作者强调，这些示踪剂还可监测亚急性期血管生成与慢性期纤维化进程，真正把卒中全周期“看透彻”。下一步需扩大临床队列、改进探针特性并与人工智能融合，让分子影像真正写进精准卒中医学诊疗常规。
Integration of these tracers across the stroke continuum—from acute perfusion to chronic repair—offers individualised read-outs for risk prediction, therapy guidance and complication assessment, and sets the stage for AI-enhanced, multimodal precision stroke medicine.
