Impact of 18F-FDOPA-PET on neurosurgery and radiotherapy of glioma patients

18F-FDOPA-PET对胶质瘤患者神经外科和放疗的影响

• 批准号: 8879067
• 负责人: Debra H Brinkmann
• 金额: $ 10.66万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-03 至 2016-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8879067
• 关键词: Adult; Amino Acids; Anatomy; Area; Biopsy; Brain; Clinic; Clinical Trials; Correlative Study; Data; Decision Making; Diagnostic; Diffusion; Diffusion Magnetic Resonance Imaging; Disease; Dose; Edema; Enhancing Lesion; Excision; Failure; Glioma; Gliosis; Gold; Health; Image; Image Enhancement; Infiltration; Intervention; Lead; Location; Magnetic Resonance Imaging; Malignant - descriptor; Nature; Non-Malignant; Normal tissue morphology; Operative Surgical Procedures; Outcome; Pathology; Patients; Pattern; Perfusion; Perfusion Weighted MRI; Planning Techniques; Positron-Emission Tomography; Primary Brain Neoplasms; Progression-Free Survivals; Protocols documentation; Radiation; Radiation therapy; Radiolabeled; Recurrence; Regimen; Research; Role; Sampling; Signal Transduction; Specimen; Staging; Survival Rate; Techniques; Testing; Therapeutic; Time; Tracer; Translating; Tumor Debulking; Tumor Pathology; Tumor Tissue; Weight; base; brain tissue; clinical practice; density; design; image guided; improved; individualized medicine; molecular imaging; neurosurgery; novel strategies; outcome forecast; pediatric patients; prospective; radiotracer; research clinical testing; tumor; uptake

DESCRIPTION (provided by applicant): Inaccurate tumor delineation due to limitations of conventional MR-based planning may contribute significantly to the dismal prognosis for gliomas. Conventional magnetic resonance imaging (MRI) currently represents the gold standard for guiding surgical debulking and radiation therapy (RT) with regions appearing abnormal on T2/FLAIR used to define the extent of tumor infiltration and regions of contrast enhancement on T1-weighted images defining regions of high tumor density. However, MRI enhancement can be inaccurate, as approximately 1/3 of non-enhancing tumors prove to be high-grade gliomas, and conversely some low-grade tumors and non-tumoral pathologies are known to enhance. While infiltrative disease is known to extend beyond areas of contrast enhancement, tumor delineation is difficult in this region due to the non-specific nature of T2 signal abnormalities which can also include gliosis and peri-tumoral edema. We hypothesize that the poor overall and progression-free survival are, in part, due to poor targeting with standard MR-based RT planning, which likely misses areas of aggressive tumor. These significant deficiencies highlight a critical need to utilize more accurate imaging-based techniques to guide surgical and RT target delineation of tumor boundaries and regions of aggressive disease. Radiolabeled amino acid tracer's shows promise for identifying aggressive disease and better differentiation between tumor and normal brain tissue. Our preliminary data suggest that 18F-DOPA PET imaging can delineate regions of high density tumor that extend beyond regions of T1 contrast enhancement and beyond T2/FLAIR abnormalities. Moreover, in non-contrast enhancing lesions seen on MRI, regions of high 18F-DOPA PET uptake correlated with highest grade of tumor. As improved survival in gliomas is associated with extent of resection, these data suggest that 18F-DOPA PET imaging may provide critical anatomic information about tumor extent not discernible on conventional MRI and could significantly improve the outcomes for patients with gliomas treated with surgery and/or radiation. Thus, this application will evaluate the impact of 18F-DOPA PET on neurosurgical targeting and RT through two clinical trials. PET thresholds for distinguishing high grade, low grade, and non-malignant portions of brain tissue will be derived from pathology correlations with stereotactically acquired specimens, and the impact of PET guidance on neurosurgical and radiotherapy planning will be evaluated through comparisons of MR vs. MR + PET treatment volumes as well as prospective evaluation of clinical outcomes in comparison with current practice. The utility of 18F-DOPA PET imaging also will be compared against state-of-the-art perfusion and diffusion tensor MRI. Ultimately, more accurate delineation of tumor extent through 18F-DOPA PET imaging may lead to increased survival associated with more complete surgical resections and more accurate targeting of radiation therapy.

描述（由申请人提供）：由于常规MR计划的局限性，肿瘤描述不准确，可能会对胶质瘤的沮丧预后产生重大贡献。常规的磁共振成像（MRI）目前代表了指导手术缓解和放射治疗（RT）的金标准，其区域在T2/Flair上似乎异常，用于定义肿瘤浸润的程度以及对T1加权图像定义高肿瘤密度的T1加权图像的对比度增强的程度。但是，MRI增强可能是不准确的，因为大约1/3的非增强肿瘤被证明是高级神经胶质瘤，相反，一些低级肿瘤和非肿瘤病理已知可以增强。尽管已知浸润性疾病超出了对比度增强区域的延伸，但由于T2信号异常的非特异性性质，在该区域很难进行肿瘤描述，这也可能包括神经胶质变化和肿瘤肿瘤性水肿。我们假设较差的整体和无进展生存率部分是由于标准MR基于RT计划的目标很差，这可能会错过侵略性肿瘤的区域。这些明显的缺陷凸显了使用更准确的基于成像的技术来指导肿瘤边界和侵袭性疾病区域的手术和RT目标描述。放射性标记的氨基酸示踪剂显示出鉴定侵袭性疾病和更好分化肿瘤和正常脑组织的希望。我们的初步数据表明，18F-DOPA PET成像可以描绘出高密度肿瘤的区域，这些区域延伸到T1对比度增强区域以及T2/Flair异常之外。此外，在MRI上看到的非对比度增强病变中，高18F-DOPA PET摄取的区域与最高级别的肿瘤相关。由于神经胶质瘤中的生存率提高与切除范围有关，因此这些数据表明18F-DOPA PET成像可能会提供有关肿瘤程度不可识别的传统MRI的关键解剖信息，并且可以显着改善接受手术和/或辐射治疗的神经胶质瘤患者的结果。因此，该应用将通过两项临床试验评估18F-DOPA PET对神经外科靶向和RT的影响。区分高级，低年级和非机敏部分的PET阈值将源自与立体标本的病理相关性，以及PET指南对神经外科和放射疗法计划的影响将通过MR + PET治疗量的比较以及与临床的预期评估相比，通过比较MR + PET治疗量来评估。还将将18F-DOPA PET成像的效用与最新的灌注和扩散张量MRI进行比较。最终，通过18F-DOPA PET成像对肿瘤范围的更准确描述可能会导致与更完整的手术切除术和更准确的放射治疗靶向相关的生存率。