Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
Department of Neurology, National Taiwan University Hospital Bei-Hu Branch, Taipei, Taiwan.
Ann Clin Transl Neurol. 2024 Feb;11(2):497-507. doi: 10.1002/acn3.51972. Epub 2023 Dec 19.
F-18-fluorothymidine (FLT) is a positron emission tomography (PET) tracer for imaging cell proliferation in vivo. We aimed to assess FLT uptake as a marker for cerebral cell proliferation in a rat model of ischemic stroke and patients with cerebral infarct, correlating with disease severity and outcomes.
Cerebral FLT PET was performed in rats subjected to transient middle cerebral artery occlusion (MCAO) and patients with cerebral infarct. PET data were analyzed and expressed as average standardized uptake value ratios (SUVRs) using cerebellar cortex as reference. Infarct volume was analyzed by 2,3,5-triphenyltetrazolium chloride staining in rats and by magnetic resonance imaging in patients. Neurological function was assessed using modified Neurological Severity Score (mNSS) for rats and National Institutes of Health Stroke Scale (NIHSS) for patients.
Seven days post-MCAO, rats' FLT PET displayed higher SUVRs in the infarcted brain, declining gradually until Day 28. FLT-binding ratio (SUVR in the infarcted brain divided by that in contralateral side) correlated positively with stroke severity (p < 0.001), and to early mNSS decline in rats with mild to moderate stroke severity (p = 0.031). In 13 patients with cerebral infarct, FLT PET showed high SUVR in the infarcted regions. FLT-binding ratio correlated positively with infarct volume (p = 0.006). Age-adjusted initial NIHSS (p = 0.035) and early NIHSS decline (p = 0.076) showed significance or a trend toward positive correlation with the FLT-binding ratio.
In vivo FLT PET detects poststroke cerebral cell proliferation, which is associated with stroke severity and/or outcomes in MCAO rats and patients with cerebral infarct.
氟代胸苷（FLT）是一种正电子发射断层扫描（PET）示踪剂，用于在体内成像细胞增殖。我们旨在评估 FLT 摄取作为缺血性卒中大鼠模型和脑梗死患者脑内细胞增殖的标志物，将其与疾病严重程度和结局相关联。
对短暂性大脑中动脉闭塞（MCAO）大鼠和脑梗死患者进行脑 FLT PET。通过小脑皮质作为参考，对 PET 数据进行分析并表示为平均标准化摄取比值（SUV）。通过 2,3,5-三苯基氯化四唑染色在大鼠中分析梗死体积，在患者中通过磁共振成像分析。使用改良神经功能缺损评分（mNSS）评估大鼠的神经功能，使用国立卫生研究院卒中量表（NIHSS）评估患者的神经功能。
MCAO 后 7 天，大鼠的 FLT PET 显示在梗死大脑中的 SUV 较高，直至第 28 天逐渐下降。FLT 结合率（梗死大脑的 SUV 除以对侧侧）与卒中严重程度呈正相关（p < 0.001），并且与轻中度卒中大鼠的早期 mNSS 下降呈正相关（p = 0.031）。在 13 例脑梗死患者中，FLT PET 显示在梗死区域的 SUV 较高。FLT 结合率与梗死体积呈正相关（p = 0.006）。年龄调整后的初始 NIHSS（p = 0.035）和早期 NIHSS 下降（p = 0.076）与 FLT 结合率呈正相关或有显著趋势。
体内 FLT PET 检测到卒中后大脑细胞增殖，与 MCAO 大鼠和脑梗死患者的卒中严重程度和/或结局相关。
