帕金森病大鼠模型细胞移植的PET在体显像研究

In vivo PET imaging of implanted cells in a Parkinson＇s disease rat model

目的探讨PET在体显示移植于帕金森病（PD）大鼠模型脑内的视网膜色素上皮（RPE）细胞分化结果及治疗效果。方法将RPE细胞移植于治疗组PD模型大鼠（12只，其中1只用于组织化学染色）纹状体内，对照组（11只）移植相同体积的生理盐水。移植前后分别进行^11C-雷氯必利（raclopride）、^11C-N-甲基-2β-甲基酯-3β-（4-F-苯基）托烷（β-CFF）PET显像，并用感兴趣区（ROI）法分析2组移植前后显像变化。移植后观察大鼠行为学改善情况及分析细胞免疫组织化学染色结果。结果移植前PET显像示大鼠模型损伤侧纹状体^11C-raclopride摄取增高，而^11C-13-CFF摄取下降。移植RPE细胞后，治疗组大鼠损伤侧纹状体^11C-raclopride摄取降低，^11C-β-CFF摄取上升。ROI分析纹状体/小脑放射性比值^11C-raclopride由1．870±0．465（移植前）降至1．601±0．257（移植后）；^11C-13．CFF由1．827±0．347（移植前）升至2．336±0．326（移植后）。大鼠旋转行为有所改善。免疫组织化学染色显示移植的RPE细胞可分化为多巴胺神经元。结论PET显像可为监测移植细胞存活、分化及转归提供一种在体、无创、可视化评价工具。

Objective It is a major hurdle for the researchers to mornitor the implanted cells＇ differentiation in vivo. This study was designed as a proof of concept of the feasibility to track the efficacy of transplanted human retinal pigment epithelial （RPE） cells in a Parkinson＇s disease （PD） rat model using PET. Methods RPE cells or normal saline were injected into striatum of the injured side of the models in treated group（ 12 rats） and control group（ 11 rats）, respectively. PET imaging on both groups was undertaken before and at certain intervals after the transplantation using ^11C-raclopride and n^11C -CFT as the markers. Behavioral observation and immunofluorescence confocal microscopy also conducted to prove PET resuits. Results PET studies showed increased ^11C-raclopride accumulation and decreased ^11C-CFF in the injured side of striatum in both groups before transplantation. The ^11C-raclopride striatum/cerebellum ratio at ipsilateral side decreased from 1. 870±0.465 to 1. 601 ±0.257 after transplantation, along with a concomitant increase of ^11C-CFT accumulation in the same area（ 1. 827±0.347 to 2.336±0.326） in treated group. The changes of PET studies paralleled the behavior states and confocal microscopic observations in the treated animals. Conclusion Even a clinical PET scanner could provide to certain extent some information on the existence and in vivo differentiation of RPE cells in a PD rat model.