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Monitoring Response to Targeted Therapy in Non-Small Cell Lung Cancer Using 18F..

使用 18F 监测非小细胞肺癌靶向治疗的反应

基本信息

批准号：
7990870
负责人：
SANJIV S GAMBHIR
金额：
$ 89.3万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-07-01 至 2015-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7990870
关键词：
Anatomy Animals Avastin Biodistribution Biological Markers Blood Blood Proteins Blood specimen Cancer Center Cancer Detection Cancer Patient Cells Chest Clinical Combined Modality Therapy Complement Data Deoxyglucose Detection Development Diagnostic EGFR inhibition Epidermal Growth Factor Receptor Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Erlotinib Evaluation Fluorine Funding Health Care Costs Human Image Imaging Device Imaging technology In Vitro Inflammatory Integrins Label Lesion Magnetism Malignant Neoplasms Malignant neoplasm of lung Measurement Methods Molecular Target Monitor Mus Nanotechnology Non-Small-Cell Lung Carcinoma Pathway interactions Patient Care Patients Performance Pharmaceutical Preparations Plasma Positron-Emission Tomography Prior Therapy Protein Microchips Protein Tyrosine Kinase Proteins Proteome RGD (sequence)Radiation Radiopharmaceuticals Recruitment Activity Sampling Scanning Serum Serum Proteins Signal Pathway Specificity Techniques Testing Time Toxic effect Tracer Transgenic Mice United States Food and Drug Administration Universities Validation Vascular Endothelial Growth Factor Receptor X-Ray Computed Tomography Xenograft procedure antiangiogenesis therapy base cancer therapy healthy volunteer human VEGF protein human subject imaging modality improved in vivo innovative technologies molecular imaging mouse model nano nanosensors novel novel strategies pilot trial pre-clinical protein profiling response sensor subcutaneous therapeutic angiogenesis tool tumor uptake

项目摘要

Fluorine-18 2-Fluoro 2-deoxyglucose ( [18] F FDG) positron emission tomography and computed tomography (PET/CT) is a powerful imaging tool for cancer detection and monitoring response to therapy in various malignancies. However, evaluation of response to therapy may be negatively influenced by its non-specificity (uptake in inflammatory/reactive cells). [18] F-labeled dimeric RGD peptide [^¿F] FPA-PEG3-E[c(RGDyK)]2 ( [18] F] FPPRGD2), a novel radiopharmaceutical recently developed at Stanford for imaging of tumor integrin expression, may provide more accurate evaluation of response to anti-angiogenesis therapy in subjects with lung cancer. We already successfully performed small animal imaging studies demonstrating the feasibility of [ [18] F] FPPRGD2 PET imaging and the possibility to monitor response to anti-angiogenesis therapy. The first in human (healthy volunteer) administration of [ [18] F] FPPRGD2 followed by PET/CT was already done on June 22, 2009. Magneto-nano protein chips (magnetic chips) enable protein profiling of mouse or human serum samples in a high throughput and multiplexed format, and represent an exciting, powerful tool for exploring many facets of the signaling pathway network in cancer. The vascular endothelial growth factor (VEGF) and human epidermal growth factor receptor (HER-1/EGFR) have been identified as key molecular targets for therapy in non-small-cell lung cancer (NSCLC). Conventional tumor imaging with contrast enhanced CT relies on changes in size to evaluate response to therapy. However, targeted therapies may not cause a significant change in the size of the lesions. Therefore, functional molecular imaging may provide earlier and more accurate means of assessing response to these new drugs. Based on the promising preliminary preclinical results we will attempt to recruit 50 subjects with NSCLC to investigate the hypotheses that [[18] F] FPPRGD2 PET/CT is feasible and that in combination with magnetonano sensors measurements of EGFR pathways can assess and predict the response to targeted Tarceva/Avastin or Vandetanib therapy in NSCLC. Aim 1: Evaluate the efficacy and feasibility of f [18] F] FPPRGD2 PET/CT scanning in patients with NSCLC. Aim 2: Evaluate the combination of [ [18] F] FPPRGD2 PET/CT and magneto-nano sensors for early assessment and prediction of response to Tarceva/Avastin or Vandetanib therapy in patients with NSCLC.

氟-18 2-氟- 2-脱氧葡萄糖（[18]fdg）正电子发射断层扫描和计算机断层扫描（PET/CT）是一种强大的成像工具，用于癌症检测和监测对各种恶性肿瘤治疗的反应。然而，对治疗反应的评估可能会受到其非特异性（炎症/反应性细胞的摄取）的负面影响。[18] F标记二聚体RGD肽[^¿F] FPA-PEG3-E[c(RGDyK)]2 （[18] F] FPPRGD2）是斯坦福大学最近开发的一种用于肿瘤整合素表达成像的新型放射性药物，可以更准确地评估肺癌患者对抗血管生成治疗的反应。我们已经成功地进行了小动物成像研究，证明了这种方法的可行性