Imaging Thymidine Uptake During Treatment for Head and Neck Cancer

头颈癌治疗期间胸苷摄取的成像

• 批准号: 7329121
• 负责人: Yusuf Menda
• 金额: $ 14.16万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-01 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7329121
• 关键词: Affect; Aftercare; American; Applications Grants; Avidity; Biopsy; Blood; Blood specimen; Breathing; Cancer Patient; Cell Cycle; Cell Cycle Kinetics; Cell Proliferation; Characteristics; Clinical; Clinical Data; Clinical Trials; Condition; DNA; Data; Detection; Diagnosis; Disease; Disease-Free Survival; Eating; Ensure; Evaluation; Exposure to; Goals; Head and Neck Cancer; Head and neck structure; Idoxuridine; Image; Image Analysis; In Vitro; Individual; Infusion procedures; Injection of therapeutic agent; Invasive; Kinetics; Label; Larynx; Malignant Neoplasms; Malignant Squamous Cell Neoplasm; Measures; Metabolic; Methodology; Methods; Morbidity - disease rate; Normal tissue morphology; Operative Surgical Procedures; Outcome; Patient Care; Patients; Pilot Projects; Positron-Emission Tomography; Predictive Value; Predictive Value of Tests; Public Health; Purpose; Radiation; Radiation therapy; Radiolabeled; Radiosurgery; Rate; Site; Squamous Cell; Staging; Techniques; Testing; Therapeutic; Thymidine; Thymidine Kinase; Time; Tissues; Toxic effect; Treatment Efficacy; Treatment Protocols; Treatment outcome; Venous; Work; analog; base; cancer site; cancer therapy; cancer type; chemotherapy; design; head and neck cancer patient; improved; innovation; killings; malignant breast neoplasm; mortality; outcome forecast; pre-clinical; radiotracer; response; tongue root; tool; treatment planning; tumor; uptake

DESCRIPTION (provided by applicant): Squamous cell cancer of the head and neck affects over 40,000 Americans each year. Treatment options for these cancers currently include surgery, radiation and chemotherapy either alone or in combination. These cancers and their treatment can have a profound impact on the ability to eat, speak, breathe and other important functions. Current treatment approaches are not uniformly successful, but all treatments produce significant morbidity. One key challenge to improving care for patients with this type of cancer is to use a treatment most likely to produce cure and least likely to produce toxicity for any individual patient. No test is available to determine which treatment approach is likely to help an individual patient. Treatment efficacy is currently determined months after completion of therapy. Preclinical and clinical data suggest changes in cell cycle kinetics following a brief exposure to radiotherapy, either alone or with chemotherapy, can be used to determine ultimate treatment efficacy in terms of locoregional control, disease free survival and overall survival. Determining changes in cell cycle kinetics involves infusion of potentially toxic analogs of DNA precursors and multiple biopsies, precluding routine assessment. Preclinical data also suggests that cell cycle kinetics can be inferred from the degree of avidity or uptake of radiolabeled DNA precursors. Work with one such precursor, 3'-deoxy, 3'[18F]Fluorolabeled Thymidine (FLT), suggests that rapidly dividing tissues have a higher avidity for FLT. The 18F label allows this agent to be imaged using Positron Emission Tomography (PET). The hypothesis of this proposal is that FLT uptake by the tumor before treatment, and changes in tumor uptake of FLT following a brief course of chemoradiotherapy will serve as predictors of ultimate response. This hypothesis will be examined in a clinical trial by specific aims designed to rigorously develop FLT PET imaging and optimize how imaging data is collected and analyzed. Dynamic FLT PET imaging will be obtained concurrently with serial venous and arterial blood sampling to ensure accurate FLT kinetic data. The optimal timing, correlations between blood analyses and image intensity and which imaging characteristics, such as mean or maximum intensity are most useful, will be determined. Using optimized FLT PET conditions, pretreatment and early mid treatment FLT studies will be obtained in subjects undergoing chemoradiation treatment for their head and neck cancer. Baseline FLT uptake values and the degree of change in FLT uptake will be tested for predictive value for overall survival and locoregional control in these subjects. The overall goal of this project is to develop a non-invasive, image-based tool to better individualize cancer therapy. FLT imaging may provide a means to individualize cancer treatment for patients with head and neck cancer allowing for more effective and less toxic therapy for patients with this disease. The relevance of this project to public health is significant. The purpose of this project is to develop a means of determining if cancer therapy is effective during the early stages of treatment, when alternative approaches can still be tried. The studies proposed here will refine and characterize a non-invasive imaging test that may allow treatment responses to be determined shortly after treatment has begun.

描述（由申请人提供）：头颈部的鳞状细胞癌每年影响40,000多名美国人。这些癌症的治疗选择包括手术，放射线和化学疗法单独或组合。这些癌症及其治疗可能会对饮食，说话，呼吸和其他重要功能的能力产生深远的影响。当前的治疗方法并非统一成功，但所有治疗方法都会产生明显的发病率。改善此类癌症患者护理的一个关键挑战是使用最有可能产生治疗的治疗方法，最不可能对任何患者产生毒性。没有测试可以确定哪种治疗方法可能有助于单个患者。治疗疗效目前是在完成治疗后几个月确定的。临床前和临床数据表明，短暂接触放疗后，单独或化疗后，细胞周期动力学的变化可用于确定最终的治疗疗效，以局部区域控制，无疾病的生存和整体存活率来确定。确定细胞周期动力学的变化涉及对DNA前体和多个活检的潜在有毒类似物的输注，从而排除了常规评估。临床前数据还表明，可以从辐射标记的DNA前体的摄取程度或吸收程度来推断细胞周期动力学。与一个这样的前体，3'-脱氧，3'[18F]氟苯甲胺（FLT）一起工作，表明迅速分裂的组织对FLT的持续性较高。 18F标签允许使用正电子发射断层扫描（PET）对该试剂进行成像。该提议的假设是，治疗前肿瘤的FLT摄取，并且在短暂的化学放放疗法后，FLT的肿瘤吸收变化将是最终反应的预测指标。该假设将在一项临床试验中以特定目的进行检查，旨在严格开发FLT PET成像，并优化如何收集和分析成像数据。动态FLT PET成像将通过串行静脉和动脉血液采样同时获得，以确保准确的FLT动力学数据。将确定最佳时机，血液分析与图像强度之间的相关性以及最有用的成像特征（例如平均值或最大强度）。使用优化的FLT PET条件，将在接受化学放疗治疗的头颈癌的受试者中进行预处理和早期治疗研究。基线FLT摄取值和FLT吸收的变化程度将测试这些受试者的总生存和局部控制的预测值。该项目的总体目标是开发一种非侵入性的，基于图像的工具，以更好地个性化癌症治疗。 FLT成像可以为患有头颈癌患者个性化癌症治疗的方法提供一种手段，从而为患有这种疾病的患者提供更有效和毒性的疗法。该项目与公共卫生的相关性很重要。该项目的目的是开发一种确定癌症治疗在治疗早期阶段是否有效的方法，即仍可以尝试替代方法。此处提出的研究将完善并表征非侵入性成像测试，该测试可能允许治疗后不久就可以确定治疗反应。