Jacobs A H, Dittmar C, Winkeler A, Garlip G, Heiss W D
Max-Planck-Institute for Neurological Research, University of Cologne, Germany.
Mol Imaging. 2002 Oct;1(4):309-35. doi: 10.1162/15353500200221392.
Gliomas are the most common types of brain tumors. Although sophisticated regimens of conventional therapies are being carried out to treat patients with gliomas, the disease invariably leads to death over months or years. Before new and potentially more effective treatment strategies, such as gene- and cell-based therapies, can be effectively implemented in the clinical application, certain prerequisites have to be established. First of all, the exact localization, extent, and metabolic activity of the glioma must be determined to identify the biologically active target tissue for a biological treatment regimen; this is usually performed by imaging the expression of up-regulated endogenous genes coding for glucose or amino acid transporters and cellular hexokinase and thymidine kinase genes, respectively. Second, neuronal function and functional changes within the surrounding brain tissue have to be assessed in order to save this tissue from therapy-induced damage. Third, pathognomonic genetic changes leading to disease have to be explored on the molecular level to serve as specific targets for patient-tailored therapies. Last, a concerted noninvasive analysis of both endogenous and exogenous gene expression in animal models as well as the clinical setting is desirable to effectively translate new treatment strategies from experimental into clinical application. All of these issues can be addressed by multi-modal radionuclide and magnetic resonance imaging techniques and fall into the exciting and fast growing field of molecular and functional imaging. Noninvasive imaging of endogenous gene expression by means of positron emission tomography (PET) may reveal insight into the molecular basis of pathogenesis and metabolic activity of the glioma and the extent of treatment response. When exogenous genes are introduced to serve for a therapeutic function, PET imaging may reveal the assessment of the "location," "magnitude," and "duration" of therapeutic gene expression and its relation to the therapeutic effect. Detailed reviews on molecular imaging have been published from the perspective of radionuclide imaging (Gambhir et al., 2000; Blasberg and Tjuvajev, 2002) as well as magnetic resonance and optical imaging (Weissleder, 2002). The present review focuses on molecular imaging of gliomas with special reference on the status and perspectives of imaging of endogenous and exogenously introduced gene expression in order to develop improved diagnostics and more effective treatment strategies of gliomas and, in that, to eventually improve the grim prognosis of this devastating disease.
神经胶质瘤是最常见的脑肿瘤类型。尽管目前正在采用复杂的传统治疗方案来治疗神经胶质瘤患者，但这种疾病最终仍会在数月或数年内导致死亡。在诸如基于基因和细胞的治疗等新的、可能更有效的治疗策略能够在临床应用中有效实施之前，必须满足某些先决条件。首先，必须确定神经胶质瘤的确切定位、范围和代谢活性，以便为生物治疗方案确定具有生物活性的靶组织；这通常通过分别对编码葡萄糖或氨基酸转运蛋白以及细胞己糖激酶和胸苷激酶基因的上调内源性基因的表达进行成像来实现。其次，必须评估周围脑组织内的神经元功能和功能变化，以避免该组织受到治疗引起的损伤。第三，必须在分子水平上探索导致疾病的特征性基因变化，以便作为针对患者的个性化治疗的特定靶点。最后，需要对动物模型以及临床环境中的内源性和外源性基因表达进行协同的非侵入性分析，以便有效地将新的治疗策略从实验转化为临床应用。所有这些问题都可以通过多模态放射性核素和磁共振成像技术来解决，并且属于分子和功能成像这个令人兴奋且快速发展的领域。通过正电子发射断层扫描（PET）对内源性基因表达进行非侵入性成像，可能有助于深入了解神经胶质瘤的发病机制、代谢活性以及治疗反应的程度。当引入外源性基因以发挥治疗功能时，PET成像可能有助于评估治疗性基因表达的“位置”“强度”和“持续时间”及其与治疗效果的关系。从放射性核素成像（Gambhir等人，2000年；Blasberg和Tjuvajev，2002年）以及磁共振和光学成像（Weissleder，2002年）的角度已经发表了关于分子成像的详细综述。本综述重点关注神经胶质瘤的分子成像，特别提及内源性和外源性引入基因表达成像的现状和前景，以便开发改进的诊断方法和更有效的神经胶质瘤治疗策略，并最终改善这种毁灭性疾病的严峻预后。
