PROGNOSTIC RADIOLOGY AND THE PATHOPHYSIOLOGY OF TUMORS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 本研究的目的是全面了解与肿瘤生长、发展和治疗反应有关的肿瘤生理学。一些非核磁共振方法，如光学技术正在开发中，然而，我们继续进行与测量氧分压和酶激活相关的磁共振工作。具体地说，我们将开发、演示和评估一种评估肿瘤氧合的新方法，以期快速应用于临床。我们认为这将与前列腺癌等疾病的大剂量低分割放射治疗最为相关。DOCUNT(由核磁共振T1和T2*评估的动态氧气挑战)利用BOLD(血氧水平依赖)和TELD(组织氧水平依赖)，与使用质子MRI非侵入性检测肿瘤氧合变化形成对比。我们建议开发一种强有力的预后检测方法来揭示肿瘤的缺氧情况。 虽然这里建议的研究完全是临床前的，但我们相信它们将证明在患者身上快速实施的强大理由。目的1通过与19F磁共振血氧测定仪的比较，严格证明DOUMENT将肿瘤分类为低氧(耐药或敏感)或氧化的能力。目的2将检查DONCENT是否确实能预测皮下生长的前列腺癌对低分割放射治疗的反应。AIM 3将把研究扩展到原位前列腺癌。AIM 4将寻求通过包括辐射增强来克服缺氧肿瘤的治疗阻力。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The goal of this research is to gain a comprehensive understanding of tumor physiology as related to tumor growth, development and response to therapy. A number of nonNMR approaches such as optical techniques are under development, However, we continue to pursue our MRI efforts related to measurement of oxygen tension and enzyme activation. Specifically, we will develop, demonstrate, and evaluate a novel approach to assessing tumor oxygenation with a view to rapid translation to the clinic. We believe it will be most pertinent to high dose hypofractionated radiotherapy in diseases such as prostate cancer. DOCENT (Dynamic Oxygen Challenge Evaluated by NMR T1 and T2*) exploits BOLD (blood oxygen level dependent) and TOLD (tissue oxygen level dependent) contrast to non-invasively detect changes in tumor oxygenation using proton MRI. We propose to develop DOCENT as a robust prognostic test to reveal tumor hypoxia. While the investigations proposed here are entirely pre-clinical, we believe they will demonstrate a strong rationale for rapid implementation in patients. Aim 1 will rigorously demonstrate the ability of DOCENT to categorize tumors as hypoxic (resistant or responsive) or oxic by comparison with 19F MR oximetry. Aim 2 will examine whether DOCENT does indeed predict response to hypofractionated radiation in subcutaneously growing prostate tumors. Aim 3 will extend studies to orthotopic prostate tumors. Aim 4 will seek to overcome therapeutic resistance of hypoxic tumors by including a radiation boost.