Imaging Thymidine Uptake During Treatment for Head and Neck Cancer

描述(申请人提供)：头颈部鳞状细胞癌每年影响40,000多名美国人。目前，这些癌症的治疗选择包括手术、放射和化疗，要么单独进行，要么联合进行。这些癌症及其治疗可以对进食、说话、呼吸和其他重要功能产生深远影响。目前的治疗方法并不总是成功的，但所有的治疗方法都会产生显著的发病率。改善对这类癌症患者的护理的一个关键挑战是使用一种最有可能治愈、最不可能对任何单个患者产生毒性的治疗方法。目前还没有测试来确定哪种治疗方法可能对个别患者有帮助。目前，治疗效果是在治疗完成几个月后确定的。临床前和临床数据表明，在短暂接受放射治疗后，细胞周期动力学的变化，无论是单独或联合化疗，都可以用来确定局部控制、无病生存和总生存的最终治疗效果。确定细胞周期动力学的变化涉及注入潜在毒性的DNA前体类似物和多次活检，排除了常规评估。临床前数据还表明，细胞周期动力学可以从亲和力或摄取放射性标记DNA前体的程度来推断。使用这样的前体，3‘-脱氧，3’[18F]氟标记胸苷(Flt)，表明快速分裂的组织对Flt有更高的亲和力。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。这一建议的假设是，肿瘤在治疗前摄取Flt，以及在短暂的放化疗后肿瘤摄取Flt的变化将作为最终疗效的预测指标。这一假设将在临床试验中得到检验，具体目的是严格开发Flt PET成像并优化成像数据的收集和分析方式。动态Flt PET成像将与连续的静脉和动脉采血同时进行，以确保准确的Flt动力学数据。将确定最佳时机、血液分析和图像强度之间的相关性以及哪些成像特征，如平均或最大强度最有用。使用优化的Flt PET条件，将在接受头颈癌的化疗放射治疗的受试者中进行前期和早期治疗的Flt研究。将测试基线Flt摄取值和Flt摄取的变化程度，以预测这些受试者的总体生存和局部区域控制的价值。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成像可能为头颈癌患者提供个体化癌症治疗的手段，从而为这种疾病的患者提供更有效和毒性更低的治疗。该项目与公共卫生的关联性很大。该项目的目的是开发一种方法，以确定癌症治疗在治疗的早期阶段是否有效，届时仍可尝试替代方法。这里提出的研究将改进和描述一种非侵入性成像测试，该测试可能允许在治疗开始后不久确定治疗反应。

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.