ENHANCED MRI FOR TUMOR VASCULAR INTEGRITY AND PERFUSION

增强对比度的药物可以提高诊断效果 增强对比度的质子磁共振成像(MRI) 正常组织和异常组织之间的差异以及通过提供 在实验室实验和人类中显示的功能信息 审判。这项提案的总体目标是在 对比测试FDA批准的磁共振造影剂(Gd-DTPA) 地葡胺)和几个具有改进潜力的新化合物 肿瘤成分和功能的特征。特异性肿瘤 要评估的特征包括可存活的和 坏死性肿瘤成分、供血血管、血容量、相对 血流灌注、毛细血管通透性和治疗引起的变化。这个 拟议研究的设计包括动物成像研究，以 确定一系列顺磁性Gd-螯合物的有效性 分子量在550到92,000道尔顿之间的衍生物。 这些大分子化合物被设计成能够产生异常高的剂量 并可作为异常毛细血管通透性的探针。 候选药物也将被测试和比较剂量的特性 有效性、稳定性、渗透压、代谢和诊断 希望定义一种或多种临床有用药物的有效性。 癌、肉瘤和淋巴瘤模型的增强特征 将其与正常组织和炎症性病变进行比较。这个 对比增强成像在肿瘤治疗反应中的应用 在荷瘤动物身上进行评估，接受辐射或 化疗。拟议的调查需要合并 诊断想象、合成化学、核磁共振物理、 药理学、核成像和放射肿瘤学。特定的 待比较的化合物包括：a)Gd-DTPA双葡胺，b)Gd-DTPA-N- 新型低渗剂甲基丙二醇，c)白蛋白-(Gd-DTPA d) 蛋白质类(Gd-DTPA，和3)(Gd-DTPA)标记的多糖核酸。 长期目标是开发新的成像策略和新的试剂。 对比度增强的磁共振成像将改善诊断 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.