Department of Nuclear Medicine, Huashan Hospital, Fudan University, No. 12 Urumchi Middle Road, Jing'an District, Shanghai, 200040, China.
Department of Radiology and Medical imaging, University of Virginia, Charlottesville, VA, 22908, USA.
Mol Imaging Biol. 2020 Oct;22(5):1161-1169. doi: 10.1007/s11307-019-01443-1.
Diabetic retinopathy (DR) is characterized by dopaminergic neuron loss in the retina of the eyes. [F]fluoropropyl-(+)-dihydrotetrabenazine ([F]FP-(+)-DTBZ) positron emission tomography (PET) has been shown to detect dopaminergic neuron loss. The study is to investigate the feasibility of PET imaging with [F]FP-(+)-DTBZ for early diagnosis of diabetic retinopathy (DR) in diabetes mellitus (DM) rat models.
The DM rat model was established by a single intraperitoneal injection of streptozotocin (STZ) (65 mg/kg). After 4 weeks, 8 weeks, and 12 weeks of STZ injection, the retinas of the rats were evaluated by electroretinogram (ERG), color fundus photography (CFP), fundus fluorescein angiography (FFA), and small animal PET scan with [F]FP-(+)-DTBZ by targeting vesicular monoamine transporter 2 (VMAT2). [F]FP-(+)-DTBZ uptake in retina was quantified as standardized uptake value (SUV). Immunofluorescence staining and Western blot were also performed to confirm the expression level of VMAT2 in retina.
ERG dysfunction was observed at 8 weeks in STZ-diabetic rats, evidenced by smaller amplitudes of oscillatory potentials (OPs) when compared with OPs in normal rats. CFP and FFA showed no significant difference in vascular leakage and neovascularization between STZ-diabetic retinas and normal ones until 8 weeks. PET imaging revealed that the SUV of [F]FP-(+)-DTBZ was significantly lower in the STZ-diabetic retinas compared with the normal ones as early as of week 4. The results from immunofluorescence staining and Western blots confirmed the early findings in PET imaging studies.
Early DR can be non-invasively detected with PET imaging using [F]FP-(+)-DTBZ targeting VMAT2. The expression level of VMAT2 in retina may act as a new biomarker for early DR diagnosis.
糖尿病性视网膜病变（DR）的特征是眼睛视网膜中的多巴胺能神经元丧失。[F]氟丙基-（+）-二氢四苯并嗪（[F]FP-（+）-DTBZ）正电子发射断层扫描（PET）已被证明可检测多巴胺能神经元的丧失。本研究旨在探讨用[F]FP-（+）-DTBZ 进行 PET 成像检测糖尿病模型大鼠糖尿病性视网膜病变（DR）早期的可行性。
采用单次腹腔注射链脲佐菌素（STZ）（65mg/kg）建立 DM 大鼠模型。STZ 注射后 4 周、8 周和 12 周，用电视网膜电图（ERG）、眼底彩色照相（CFP）、眼底荧光血管造影（FFA）和小动物[F]FP-（+）-DTBZ PET 扫描评估大鼠视网膜，以靶向囊泡单胺转运体 2（VMAT2）。视网膜[F]FP-（+）-DTBZ 摄取量用标准化摄取值（SUV）表示。还进行了免疫荧光染色和 Western blot 以证实视网膜中 VMAT2 的表达水平。
STZ 糖尿病大鼠在 8 周时出现 ERG 功能障碍，表现为与正常大鼠相比，振荡电位（OP）的振幅较小。CFP 和 FFA 显示，STZ 糖尿病视网膜的血管渗漏和新生血管化与正常视网膜相比，直到 8 周时才出现显著差异。PET 成像显示，早在 4 周时，[F]FP-（+）-DTBZ 的 SUV 在 STZ 糖尿病视网膜中明显低于正常视网膜。免疫荧光染色和 Western blot 的结果证实了 PET 成像研究中的早期发现。
使用靶向 VMAT2 的[F]FP-（+）-DTBZ 进行 PET 成像可以无创检测早期 DR。视网膜中 VMAT2 的表达水平可能成为早期 DR 诊断的新生物标志物。
