EVALUATION OF THERAPY FOR BREAST CANCER USING PARACEST MRI

这个子项目是许多利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他CRISP条目中表示。所列机构为 中心，但不一定是研究者所在的机构。 根据美国癌症协会2004年的统计数据，乳腺癌仍然是美国妇女癌症死亡的第二大原因。具有高灵敏度和特异性的检测技术也将降低目前乳腺肿块妇女的高阴性活检率，并有助于定制个性化的治疗方案。用常规小分子造影剂增强的乳腺磁共振成像（MRI）对乳腺癌检测具有高灵敏度，但对检测到的病变的表征具有有限的特异性。使用大分子（大分子）造影剂的类似方法可以提供这种组织分化，但灵敏度较低。不能同时使用这两种药剂，因为无法区分两者的效果。一类新的造影剂，称为“PARACEST剂”，最近已提出用于MRI应用，并迫切需要在体内进行评估，因为理论上预测的灵敏度，这些代理是高于传统的Gd为基础的代理。这些试剂还具有使用射频脉冲随意开启图像对比度的优点。我们计划研究这种大分子PARACEST试剂白蛋白-EuDOTA-4Am-（Gly）2（OBz-Ser）2在大鼠肿瘤中的动力学，随后施用常规小分子造影剂Gd-DTPA。这两种试剂使用不同的机制影响图像对比度，因此在Gd-DTPA之前给予PARACEST试剂不会影响随后的Gd-DTPA对比度。本课题的具体目标是：1）优化PARACEST成像序列和对比度参数。2)研究肌肉组织和肿瘤中动态PARACEST对比增强（DPCE）动力学，并建立动力学模型。3)使用DPCE动力学研究两种肿瘤细胞系对抗血管生成治疗的反应。

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. Breast cancer continues to be the second leading cause of cancer deaths in American women according to American Cancer Society statistics for 2004. A detection technique with high sensitivity and specificity would also decrease the current high rate of negative biopsies of women with breast masses and help tailor individualized therapeutic options. Magnetic resonance imaging (MRI) of the breast enhanced with conventional, small molecular contrast agent has a high sensitivity for breast cancer detection but a limited specificity for the characterization of the detected lesions. A similar approach, which uses large molecular (macromolecular) contrast agents, can provide this tissue differentiation but the sensitivity is low. One cannot use these two types of agents together as it would be impossible to distinguish between effects of the two. A novel class of contrast agents, called "PARACEST agents", have been recently proposed for MRI applications and need to be urgently evaluated in vivo as the theoretically predicted sensitivity of these agents is higher than conventional Gd-based agents. These agents also have the advantage of having image contrast turned on at will using radio-frequency pulses. We planned to study the kinetics of such a macromolecular PARACEST agent albumin-EuDOTA-4Am-(Gly)2(OBz-Ser)2 in rat tumors and subsequently administer a conventional small molecular contrast agent Gd-DTPA. These two agents affect the image contrast using different mechanisms and hence administering the PARACEST agent before Gd-DTPA will not affect the subsequent Gd-DTPA contrast. Specific aims of this project are: 1) Optimization of PARACEST imaging sequence and contrast parameters. 2) Study dynamic PARACEST contrast enhancement (DPCE) kinetics in muscle tissue and tumors and develop kinetic model. 3) Use DPCE kinetics to study response to antiangiogenic therapy in two tumor lines.