PROGNOSTIC RADIOLOGY AND THE PATHOPHYSIOLOGY OF TUMORS

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目及 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 本研究的目的是全面了解肿瘤生理学与肿瘤生长、发展和治疗反应的关系。 一些非核磁共振方法，如光学技术正在开发中，然而，我们继续追求我们的MRI努力与测量的氧张力和酶的活化。 具体来说，我们将开发，演示和评估一种新的方法来评估肿瘤氧合，以期快速转化为临床。我们相信，它将是最相关的高剂量低分割放射治疗的疾病，如前列腺癌。DOCENT（通过NMR T1和T2* 评估的动态氧挑战）利用BOLD（血氧水平依赖性）和TOLD（组织氧水平依赖性）对比度，使用质子MRI无创检测肿瘤氧合的变化。我们建议开发DOCENT作为一个强大的预后测试，以揭示肿瘤缺氧。 虽然本文提出的研究完全是临床前研究，但我们相信它们将证明在患者中快速实施的有力依据。目标1将通过与19 F MR血氧测定法进行比较，严格证明DOCENT将肿瘤分类为缺氧（耐药或反应性）或氧化的能力。目的2将检验DOCENT是否确实预测皮下生长的前列腺肿瘤对大分割放射的反应。目标3将研究扩展到原位前列腺肿瘤。目标4将寻求通过加强辐射来克服缺氧肿瘤的治疗抵抗力。

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.