ENHANCED MRI FOR TUMOR VASCULAR INTEGRITY AND PERFUSION

对比增强药物可以提高诊断的好处， 质子增强磁共振成像 正常和异常组织之间的差异，并通过提供 如实验室实验和人体实验中所示的功能信息 审判 本提案的总体目标是评估 比较测试了FDA批准的MRI造影剂（Gd-DTPA）和 二甲葡胺）和几种具有改善的潜力的新型化合物。 肿瘤组成和功能的表征。 特异性肿瘤 要评估的特征包括可行的和 坏死肿瘤成分，供血血管，血容量，相对 灌注、毛细血管通透性和治疗引起的变化。 的 拟议研究的设计包括动物成像研究， 定义一系列顺磁性钆螯合物的功效 分子量范围为550至92，000道尔顿的衍生物。 高分子化合物被设计成产生异常高的剂量 有效性，并作为异常毛细血管通透性的探针。 候选药物也将进行测试和比较的性质，剂量 有效性、稳定性、渗透压、代谢和诊断 有效性，希望定义一种或多种临床上有用的药物。 癌、肉瘤和淋巴瘤模型中的增强特征 将与正常组织和炎性病变进行比较。 的 用于肿瘤治疗反应的对比增强成像的效用将 在接受辐射或放射治疗的荷瘤动物中进行评估， 化疗 拟议的调查需要 诊断成像，合成化学，核磁共振物理， 药理学、核成像和放射肿瘤学。 具体 比较的化合物包括：a）Gd-DTPA二葡甲胺，B）Gd-DTPA-N- 甲基丙二醇，一种新的低渗剂，c）白蛋白-（Gd-DTPA d） 类蛋白-（Gd-DTPA）和3）（Gd-DTPA）-标记的多糖。 长期目标是开发新的成像策略和新的药物 对比增强MRI可以提高诊断 肿瘤和肿瘤治疗的评估。

Contrast enhancing pharmaceuticals can improve the diagnostic benefit of proton magnetic resonance imaging (MRI) by increasing contrast differences between normal and abnormal tissues and by providing functional information as shown in laboratory experiments and human trials. The general objectives of this proposal are to evaluate in comparison tests both a FDA-approved MRI contrast agent (Gd-DTPA dimeglumine) and several novel compounds with potential for improved characterization of tumor composition and function. Specific tumor characteristics to be assessed include differences between viable and necrotic tumor components, feeding vascularity, blood volume, relative perfusion, capillary permeability, and changes induced by therapy. The design of the proposed research includes animal imaging studies to define the efficacy of a series of paramagnetic gadolinium-chelate derivatives ranging in molecular weights from 550 to 92,000 Daltons. The macromolecular compounds are designed to produce unusually high dose effectiveness and to serve as probes of abnormal capillary permeability. Candidate drugs will also be tested and compared for properties of dose effectiveness, stability, osmolality, metabolism and diagnostic effectiveness in hopes of defining one or more clinically useful drug. Enhancement characteristics in carcinoma, sarcoma, and lymphoma models will be compared to normal tissues and inflammatory lesions. The utility of contrast enhanced imaging for tumor treatment response will be assessed in tumor-bearing animals receiving either radiation or chemotherapy. The proposed investigations require the combined disciplines of diagnostic imagining, synthetic chemistry, NMR physics, pharmacology, nuclear imagining, and radiation oncology. Specific compounds to be compared include: a) Gd-DTPA dimeglumine, b) Gd-DTPA-N- methylpropandiol, a novel low-osmolar agent, c) albumin-(Gd-DTPA d) proteinoid-(Gd-DTPA, and 3) (Gd-DTPA)-labeled polysaccarhides. The long term goal is to develop new imaging strategies and new agents for the contrast enhanced MRI that will improve the diagnostic evaluation of tumors and tumor therapies.