Micro-SPECT Imaging of Acute Ischemic Stroke with Radioiodinated Riboflavin in Rat MCAO Models via Riboflavin Transporter Targeting
Micro-SPECT Imaging of Acute Ischemic Stroke with Radioiodinated Riboflavin in Rat MCAO Models via Riboflavin Transporter Targeting
复制标题
通过核黄素转运蛋白靶向，在大鼠 MCAO 模型中使用放射性碘化核黄素对急性缺血性中风进行显微 SPECT 成像。
DOI：
10.1021/acschemneuro.2c00177
复制
发表时间：
2022-06-26
影响因子：
5
通讯作者：
Zhang, Xianzhong
中科院分区：
文献类型：
--
作者：
Li, Jindian;Chen, Yingxi;Zhang, Xianzhong
核黄素转运蛋白3（Riboflavin transporter-3，RFVT-3）是近年来发现的一种新的神经系统疾病诊断治疗的生物标志物。RFVT 3在缺血性卒中后的脑损伤中显著过表达。在此，我们首次报道了一种靶向RFVT 3的示踪剂I-131-核黄素（I-131-RFLA）用于体内缺血性卒中的SPECT成像。I-131-RFLA通过碘原包被法放射合成。I-131-RFLA的放射化学产率为69.2 +/- 3.7%，放射化学纯度大于95%。使用I-131-RFLA的代表性SPECT/CT图像显示，与对侧正常脑相比，脑损伤中的示踪剂摄取在卒中后1 h、3 d和7 d显著增加。离体放射自显影显示梗塞脑与正常脑的摄取比值为3.63，阻断后降至1.98，再次证实了SPECT图像的结果。重要的是，通过H&E和免疫组织化学染色确定了RFVT 3表达与脑损伤之间的显著相关性。因此，RFVT 3是一个新的和潜在的缺血性脑卒中早期诊断的生物标志物。此外，I-131-RFLA是一种很有前途的SPECT示踪剂，可用于体内RFVT 3相关缺血性脑损伤的成像。
Riboflavin transporter-3 (RFVT3) is a recently discovered and novel biomarker for the theranostics of nervous system diseases. RFVT3 is significantly overexpressed in cerebral injury after ischemic stroke. Herein, we first reported an RFVT3-targeted tracer I-131-riboflavin (I-131-RFLA) for SPECT imaging of ischemic stroke in vivo. I-131-RFLA was radiosynthesized by the iodogen-coating method. I-131-RFLA possessed a radiochemical yield of 69.2 +/- 3.7% and greater than 95% radiochemical purity. The representative SPECT/CT images using I-131-RFLA demonstrated the conspicuously increased tracer uptake in the cerebral injury by comparison with the contralateral normal brain at 1 h and 3 and 7 d after stroke. Ex vivo autoradiography demonstrated that the ratio of infarcted to normal brain uptake was 3.63 and it was decreased to 1.98 after blocking, which reconfirmed the results of SPECT images. Importantly, a significant correlation was identified between RFVT3 expression and brain injury by H&E and immunohistochemistry staining. Therefore, RFVT3 is a new and potential biomarker for the early diagnosis of ischemic stroke. In addition, I-131-RFLA is a promising SPECT tracer for imaging RFVT3-related ischemic cerebral injury in vivo.