Chen Ping, Li Jun, Li Zhan, Yu Duxia, Ma Ning, Xia Zian, Meng Xianglei, Liu Xingdang
Department of Nuclear Medicine, Peking University Shenzhen Hospital, Shenzhen, China.
Drug Clinical Trial Institution, Peking University Shenzhen Hospital, Shenzhen, China.
Ann Nucl Med. 2023 Apr;37(4):219-226. doi: 10.1007/s12149-022-01818-5. Epub 2023 Jan 6.
Noninvasive methods used in clinic to accurately detect DA neuron loss in diabetic brain injury and diabetic retinopathy have not been reported up to now. F-FP-CIT is a promising dopamine transporter (DAT) targeted probe. Our study first applies F-FP-CIT PET imaging to assess DA neuron loss in the striatum and retina of T1DM rat model.
T1DM rat model was induced by a single intraperitoneal injection of streptozotocin (STZ) (65 mg kg, ip). F-FP-CIT uptake in the striatum and retina was evaluated at 4 weeks, 8 weeks and 12 weeks after STZ injection. The mean standardized uptake value (SUVmean) and the maximum standardized uptake value (SUVmax) were analyzed. Western blot was performed to confirm the DAT protein levels in the striatum and retina.
PET/CT results showed that the SUV of F-FP-CIT was significantly reduced in the diabetic striatum and retina compared with the normal one from 4-week to 12-week (p < 0.0001). Western blots showed that DAT was significantly lower in the diabetic striatum and retina compared to the normal one for all three time points (p < 0.05). The results from Western blots confirmed the findings in PET imaging studies.
DA neuron loss in the striatum and retina of T1DM rat model can be non-invasively detected with PET imaging using F-FP-CIT targeting DAT. F-FP-CIT PET imaging may be a useful tool used in clinic for DR and diabetic brain injury diagnosis in future. The expression level of DAT in striatum and retina may act as a new biomarker for DR and diabetic brain injury diagnosis.
目前尚未有临床用于准确检测糖尿病脑损伤和糖尿病视网膜病变中多巴胺能（DA）神经元丢失的非侵入性方法的报道。F-FP-CIT是一种有前景的靶向多巴胺转运体（DAT）的探针。我们的研究首次应用F-FP-CIT正电子发射断层显像（PET）成像来评估1型糖尿病（T1DM）大鼠模型纹状体和视网膜中的DA神经元丢失情况。
通过单次腹腔注射链脲佐菌素（STZ）（65 mg/kg，腹腔注射）诱导建立T1DM大鼠模型。在注射STZ后4周、8周和12周评估纹状体和视网膜中F-FP-CIT的摄取情况。分析平均标准化摄取值（SUVmean）和最大标准化摄取值（SUVmax）。采用蛋白质免疫印迹法（Western blot）来确认纹状体和视网膜中DAT蛋白水平。
PET/CT结果显示，与正常大鼠相比，糖尿病大鼠纹状体和视网膜中F-FP-CIT的SUV在4周~12周期间显著降低（p＜0.0001）。蛋白质免疫印迹法显示，在所有三个时间点，糖尿病大鼠纹状体和视网膜中的DAT均显著低于正常大鼠（p＜0.05）。蛋白质免疫印迹法的结果证实了PET成像研究的结果。
使用靶向DAT的F-FP-CIT通过PET成像可无创检测T1DM大鼠模型纹状体和视网膜中的DA神经元丢失。F-FP-CIT PET成像未来可能是临床上用于诊断糖尿病视网膜病变（DR）和糖尿病脑损伤的有用工具。纹状体和视网膜中DAT的表达水平可能作为DR和糖尿病脑损伤诊断的新生物标志物。
