Molecular Imaging of Cancer and Its Response to Therapy

癌症的分子成像及其对治疗的反应

• 批准号: 7945682
• 负责人: Janet F. Eary
• 金额: $ 140.94万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-05-12 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7945682
• 关键词: 2' -Deoxythymidine; Aggressive behavior; Algorithms; Androgen Receptor; Androgens; Animal Model; Behavior; Biologic Characteristic; Biological; Biological Markers; Biology; Brain Neoplasms; Cancer Biology; Cancer Patient; Characteristics; Child; Clinical; Clinical Research; Clinical Trials; Clinical Trials Design; Collaborations; Communities; Data Analyses; Development; Diagnostic Neoplasm Staging; Disease; Dose; Drug Delivery Systems; ERBB2 gene; Effectiveness; Evaluation; External Beam Radiation Therapy; FPS-FES Oncogene; Failure; Funding; Future; Generic Drugs; Goals; Guidelines; Hawks; Heterogeneity; Hypoxia; Image; Image Analysis; Imaging Device; Imaging Techniques; Investigation; Kinetics; Learning; Ligands; Logistic Regressions; Magnetic Resonance Imaging; Malignant Neoplasms; Malignant neoplasm of prostate; Measures; Medicine; Methods; Modeling; Molecular Profiling; Monoamine Oxidase A; Multi-Drug Resistance; Multi-Institutional Clinical Trial; Neoadjuvant Therapy; Neoplasm Metastasis; New Agents; Normal tissue morphology; Observational Study; Operative Surgical Procedures; Outcome; P-Glycoprotein; Patient Care; Patient Rights; Patients; Pharmaceutical Preparations; Pharmacodynamics; Pharmacotherapy; Phase; Phenotype; Physiological; Play; Positron-Emission Tomography; Preparation; Procedures; Process; Prognostic Factor; Progress Reports; Progression-Free Survivals; Prostate Adenocarcinoma; Protocols documentation; Radiopharmaceuticals; Randomized Controlled Trials; Recording of previous events; Regimen; Reporting; Research; Research Design; Resistance; Risk; Role; Scheme; Site; Specific qualifier value; Structure; Systemic Therapy; Techniques; Testing; Therapeutic Agents; Thromboplastin; Time; Tissues; Translating; Translations; Tumor Oxygenation; Validation; Verapamil; Work; Writing; cancer care; cancer imaging; cell growth; chemotherapy; clinical practice; clinically significant; copper (II) diacetyl-di(N(4)-methylthiosemicarbazone); design; fluorodeoxyglucose positron emission tomography; hormone therapy; improved; in vivo; malignant breast neoplasm; molecular imaging; novel therapeutics; pre-clinical; prognostic; programs; receptor function; research and development; research study; resistance factors; response; therapeutic target; therapy resistant; treatment planning; treatment response; tumor; tumor progression; uptake; working group

This program tests molecular imaging variables, how they predict response to therapy, and how they change over the course of different treatments. We propose 5 interactive projects: 1. Proliferation studies to validate how well FLT compares to TdR in patients with a variety of tumors and explores ways to simplify the PET procedure and still distinguish flux from transport. Our hypothesis is that FLT with appropriate data analysis can be as accurate as TdR for reporting tumor proliferation. We will test the hypothesis that FLT PET plus MRI can distinguish between tumor progression and pseudoprogression in patients with GBM that finish initial therapy with external beam RT plus concurrent TMZ. 2. Tumors have variable levels of multi-drug resistance that reduces effectiveness of drug treatments. We will quantify transporter activity of P-glycoprotein as a suspected cause of treatment resistance and failure by analyzing [11C]-verapamil kinetics. We will test the hypothesis that pts who up-regulate their tumor Pgp activity after neoadjuvant chemotherapy will have shorter survival and time to progression. 3. Hypoxia is an important resistance factor that is imaged using [18F]-FMISO. In pts with brain tumors we will test the hypothesis that FMISO images following initial surgery define an appropriate target for focal boost RT that will improve time to tumor progression and survival. In pts with ER-neg metastatic breast cancer, we will compare the extent of hypoxia to response to systemic therapy and progression-free survival. Other experiments will compare FMISO and [64Cu]-ATSM and we will measure temporal changes using an FMISO test-retest protocol and BOLD-MRI to look for short term changes in regional oxygenation of tumors. 4. This project will test the use of 18F-FES PET to choose therapy in pts with a history of ER+ breast cancer who have failed prior regimens and are being considered for salvage endocrine therapy and use FES PET to measure regional ER as a pharmacodynamic response to endocrine therapy and FDG PET to localize active tumor and identify early effects of drug therapy, including HER2 and ER. The project will also image androgen receptor function in prostate cancer to identify heterogeneous AR expression. 5. Preclinical radiopharmaceutical development and research. New methods will be developed to image important aspects of the tumor phenotype. Some are new molecules; some are new applications for old molecules; all to develop promising imaging agents for characterizing the tumor phenotype. These include ligands for HER2 as a factor in treating breast cancer, new agents for imaging of androgen biology, a monoamine oxidase A ligand to select patients for a new clinical trial for prostate adenocarcinoma and studies comparing Cu-ATSM and FMISO for different mechanisms of uptake.

该程序测试了分子成像变量，它们如何预测对治疗的反应以及它们在不同治疗过程中的变化。我们提出了5个互动项目：1。增殖研究，以验证各种肿瘤患者的FLT与TDR的比较，并探讨了简化PET程序并仍然将通量与转运区分开的方法。我们的假设是，具有适当数据分析的FLT可以像报告肿瘤增殖一样准确。我们将检验以下假设：FLT PET PLES PLE MRI可以区分GBM患者的肿瘤进展和伪雌性，这些患者使用外束RT加上并发的TMZ结束初始治疗。 2。肿瘤具有可变水平的多药耐药性，可降低药物治疗的有效性。我们将通过分析[11C] - verapamil动力学来量化P-糖蛋白的转运蛋白活性，作为可疑的治疗耐药性和衰竭原因。我们将检验以下假设：新辅助化疗后上调其肿瘤PGP活性的PT将具有更短的生存和进展时间。 3。缺氧是使用[18F] -fmiso成像的重要抗性因子。在患有脑肿瘤的PT中，我们将测试以下假设：初次手术后的FMISO图像定义了局灶性增强RT的适当靶标，这将改善肿瘤进展和存活的时间。在患有ER-NEG转移性乳腺癌的PT中，我们将比较缺氧对全身治疗和无进展生存的反应的程度。其他实验将比较FMISO和[64CU] -ATSM，我们将使用FMISO测试 - 重测方案和BOLD-MRI测量时间变化，以寻找肿瘤区域氧合的短期变化。 4。该项目将测试使用18F-FES PET选择具有ER+乳腺癌病史的PT中的治疗，这些PTS疗法未通过先前的治疗疗法，并被考虑用于抢救内分泌疗法，并使用FES PET来测量区域性ER作为对内分泌疗法的药物学反应，对内分泌治疗和FDG PET进行了局部化肿瘤，以局部化肿瘤和早期疗法的药物治疗，包括医生2和ER。该项目还将在前列腺癌中成像雄激素受体功能，以鉴定异质AR表达。 5。临床前放射药物的发展和研究。将开发新方法来图像肿瘤表型的重要方面。有些是新分子；有些是旧分子的新应用；所有人都开发出有希望的成像剂来表征肿瘤表型。其中包括HER2的配体作为治疗乳腺癌的一个因素，雄激素生物学成像的新剂，一种单胺氧化酶是配体，用于选择患者进行新的临床试验，以进行前列腺腺癌的新临床试验以及比较Cu-ATSM和FMISO的研究。