EVALUATION OF ANTIANGIOGENIC THERAPY OF BREAST CANCER USING PARACEST MRI

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。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。这突出表明需要研究乳腺癌检测技术，以便在疾病的早期阶段进行检测和治疗。一种具有高灵敏度和特异性的检测技术也将降低目前乳房肿块妇女的高阴性活组织检查率，并有助于定制个性化的治疗方案。乳房磁共振成像（MRI）采用传统的T1改变小分子造影剂增强，对乳腺癌检测具有很高的敏感性，但对检测到的病变特征的特异性有限。传统的大分子造影剂有可能提供这种组织分化，但灵敏度较低。不能同时使用这两种药剂，因为不可能区分这两种药剂的效果。一类基于化学交换饱和转移（CEST）效应的顺磁造影剂最近被提出用于MRI应用。这种新型的“PARACEST”造影剂迫切需要在体内进行评估，特别是因为理论上预测这些造影剂的敏感性高于传统的基于gd的造影剂。由于与Gd-DTPA相比，其T1弛豫度非常低，因此其给药不会影响随后在同一受试者上进行的Gd-DTPA研究。

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. This highlights the need for research in breast cancer detection techniques to facilitate detection and treatment at an early stage in the disease. 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, T1 altering, small molecular contrast agents have a high sensitivity for breast cancer detection but a limited specificity for characterization of the detected lesions. Conventional macromolecular contrast agents have the potential to 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 paramagnetic contrast agents based on the chemical exchange saturation transfer (CEST) effect has been recently proposed for MRI applications. This new class of ¿PARACEST¿ contrast agents needs to be urgently evaluated in vivo especially since the theoretically predicted sensitivity of these agents is higher than conventional Gd-based agents. Due to its very low T1 relaxivity compared to Gd-DTPA, its administration will not affect a Gd-DTPA study performed on the same subject subsequently.