EVALUATION OF THERAPY FOR BREAST CANCER USING PARACEST MRI

这个子项目是众多研究子项目之一

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.