胶质瘤脑灌注MRI和18F-Chlorotoxin PET双模式显像

Early diagnosis of high-grade glioma, definition of tumor margin and monitoring treatment effect have been a key problem to be solved urgently. The applicant's previous work have preliminary confirmed that on basis of T1 weighted dynamic contrast-enhanced MRI (T1DCE-MRI) technology, microvascular permeability parameters (Ktrans) of glioma has been quantitatively measured through double compartment model for preoperative glioma grading. In order to target tumor cells, this project is aimed to use 18F-SFB (N-succinimidyl 4-[18F]fluorobenzoate) which has been already automatically synthesized, labeling small molecule polypeptide Chlorotoxin to synthesize new glioma specific targeting PET (positron emission tomography) agents. 18F-Chlorotoxin, which has high affinity with matrix metalloproteinase-2 expressed by glioma cell, so it is able to target tumor cells and become a new molecular probe. MR perfusion and 18 F-Chlorotoxin PET are performed on tumor-bearing nude mice model. The images of MRI and PET in DICOM (digital imaging and communications in medicine) format are fused through Matlab platform, so high resolution images of fine anatomical structures with function (PET/MRI) were acquired, which called dual-modality imaging. This will be compared with histopathological results to evaluate sensitivity, specificity and accuracy of tumor detection. Dual-modality imaging will provide a new technology and method for gliomas diagnosis, and has an important clinical value in early diagnosis of gliomas, tumor boundary definition, curative effect evaluation and targeted drugs transportation.

高级别胶质瘤的早期诊断，肿瘤边界的确定，治疗效果的监测一直是亟需解决的关键问题。申请者既往工作基础初步证实，T1加权动态对比增强MRI技术可定量血脑屏障渗透性参数Ktrans，通过评估肿瘤微血管的渗透性进而对胶质瘤进行术前无创性分级。为了能靶向显示肿瘤，本课题在已合成放射核素标记多肽的前体18F-SFB的基础上，用18F-SFB标记小分子多肽Chlorotoxin，制备新型PET显像剂18F-Chlorotoxin，它可以与胶质瘤细胞表面高表达的金属基质蛋白酶MMP-2高亲和性结合，靶向显示肿瘤。利用负瘤裸鼠进行MRI灌注及18F－ChlorotoxinPET成像，将MRI和PET图像融合，获得具有精细解剖结构兼功能的PET/MRI图像（双模式显像），并与组织病理对照，研究其显示肿瘤的敏感性、特异性和准确性。双模式显像将为胶质瘤的早期诊断、肿瘤边界的界定及疗效评价等方面发挥重要的临床价值。

高级别胶质瘤的早期诊断，肿瘤边界的确定，治疗效果的监测一直是亟需解决的关键问题。本项目通过联合多种高级功能性MRI成像，灌注成像（动态对比增强MRI-T1DCE-MRI），扩散成像(扩散张量成像DTI，扩散峰度成像DKI，氨基质子转移成像APT对胶质瘤进行多模式显像。多参数（Ktrans，FA, MD, λ||, λ⊥, MK, K||, K⊥）定量评估脑胶质瘤的无创性分级、手术边界和监测治疗效果。联合多种高级功能性MRI成像已证实它们可以对胶质瘤进行术前无创性分级，并于脑内其它肿瘤鉴别。在此基础上，同时利用小分子多肽Chlorotoxin，研制新型靶向胶质瘤PET显像剂18F-Chlorotoxin，它可以与胶质瘤细胞表面高表达的金属基质蛋白酶MMP-2高亲和性结合,靶向显示肿瘤，制成分子探针，本项目中18F-Chlorotoxin已经顺利合成。利用负瘤裸鼠模型进行MR灌注成像及18F-Chlorotoxin PET成像，将MRI和PET图像经后处理软件融合，获得具有精细解剖结构兼功能图像的PET/MRI图像，并与组织病理对照，研究其显示肿瘤的敏感性、特异性和准确性。本课题的目的是为胶质瘤的诊断提供一种全新的技术方法，并将在胶质瘤的早期诊断、界定肿瘤边界、疗效评价及靶向药物的输送等方面具有重要的临床价值，做到早期、精准、靶向及个体化治疗胶质瘤。