Project:
Improved Detection of Breast Cancer With Folate Receptor-Targeted Contrast Agents for MR Imaging

Principal Investigator - Heike Daldrup-Link, MD, PhD

ABSTRACT

The purpose of this study is to improve the diagnosis of breast cancers with a novel folate-receptor (FR) targeted contrast agent for magnetic resonance (MR) imaging. FRs are present in high quantities on the surface of breast cancer cells, but not or only to a minor degree on cells of normal organs. Our hypothesis is that FR-targeted contrast agents provide an exclusive signal enhancement of breast cancers, but not normal organs, thereby improving tumor detection and characterization. Studies will be performed on cell cultures and in rats with implanted human breast cancers. Human breast cancer cells will be incubated with the new FR-specific contrast agent. The presence of FR on the tumor cell surface will be visualized with histopathology and compared with the signal enhancement of the cells on MR images as well as the contrast agent uptake into the tumor cells, as quantified by spectrometry. Subsequent studies in rats with implanted human breast cancers will be performed after intravenous injection of the FR-specific contrast agent. Control experiments on FR-negative lung cancers should confirm absence of contrast enhancement in those tumors. The signal enhancement of FR-positive breast cancers on MR images after injection of the FR-targeted contrast agent will be quantified and compared with the degree of FR-expression of the tumors, as determined by histopathology. The proposed research should help to improve the diagnosis of breast cancers with new, tumor-specific contrast agents for MR imaging. This could lead to an earlier diagnosis of small breast cancers, better differentiation of breast cancers from normal tissues, better detection of metastases and improved delineation of tumor recurrence. The described contrast agent and MR imaging techniques are in principle clinically applicable. We plan a subsequent investigational drug application in order to make this new agent accessible to breast cancer patients.