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: 8916555
• 负责人: KENNETH A. KROHN
• 金额: $ 136.44万
• 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 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8916555
• 关键词: 2' -Deoxythymidine; Aggressive behavior; Algorithms; Androgen Receptor; Androgens; Animal Model; Behavior; Biologic Characteristic; Biological; 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; Metastatic breast cancer; 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; imaging agent; imaging biomarker; improved; in vivo; malignant breast neoplasm; molecular imaging; novel therapeutics; personalized medicine; pre-clinical; predictive modeling; 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.

该程序测试分子成像变量，它们如何预测治疗反应，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Flt与TDR在各种肿瘤患者中的比较情况，并探索简化PET程序并仍能区分流量和传输的方法。我们的假设是，在进行适当的数据分析后，FLT在报告肿瘤增殖方面可以与TDR一样准确。我们将验证这样一种假设，即Flt PET加MRI可以区分完成外放射治疗加TMZ初步治疗的GBM患者的肿瘤进展和假性进展。2.肿瘤具有不同程度的多药耐药，这降低了药物治疗的有效性。我们将通过分析[11C]-维拉帕米的动力学来量化P-糖蛋白的转运蛋白活性，将其作为治疗耐药和失败的可疑原因。我们将检验这样一种假设，即在新辅助化疗后上调肿瘤Pgp活性的患者将有较短的生存期和进展时间。3.低氧是一个重要的阻力因子，用[18F]-FMISO成像。在脑肿瘤患者中，我们将检验这样一种假设，即初始手术后的FMISO图像为焦点增强RT定义了合适的靶点，这将改善肿瘤进展和生存的时间。在ER阴性的转移性乳腺癌患者中，我们将比较全身治疗反应和无进展生存期的缺氧程度。其他实验将比较FMISO和[64Cu]-ATSM，我们将使用FMISO测试-重新测试协议和BOLD-MRI来测量时间变化，以寻找肿瘤局部氧合的短期变化。4.这个项目将测试18F-FES PET在有ER+乳腺癌病史的患者中选择治疗的使用，这些患者以前的治疗方案失败，正在考虑挽救内分泌治疗，并使用FES PET来测量局部ER作为内分泌治疗的药效反应，使用FDG PET来定位活动性肿瘤，并确定药物治疗的早期效果，包括HER2和ER。该项目还将成像前列腺癌中雄激素受体的功能，以确定AR的异质性表达。5.临床前放射性药物的开发和研究。将开发新的方法来对肿瘤表型的重要方面进行成像。有些是新分子；有些是旧分子的新应用；所有这些都是为了开发有希望的成像试剂来表征肿瘤的表型。这些包括用于治疗乳腺癌的HER2的配体，用于雄激素生物学成像的新试剂，用于为前列腺癌的新临床试验选择患者的单胺氧化酶A配体，以及比较铜-ATSM和FMISO不同摄取机制的研究。