Contrast Agents for Breast Cancer Diagnosis by Magnetic Resonance Imaging: Targeting the Folate Receptor

摘要

Folate receptors are overexpressed on a variety of human cancer cells, including breast cancer cells, but are restricted in normal tissues. Folate-conjugated radiopharmaceuticals have shown specificity for folate- receptor-bearing cells and promise in cancer imaging in animal models. We proposed to explore the coupling to folate of a series of MR contrast agents whereby ligands for complexation of paramagnetic metal ions, such as iron(III) and gadolinium(III) would be attached to folate and hence targeted to cancer cells. Folate- coupled ligands for these paramagnetic ions proved to be insufficiently soluble in aqueous media for separation, purification and utilization at the concentrations required for imaging purposes. In order to increase water solubility, poly(ethylene glycol) spacer units were incorporated into the conjugates and it was found that water soluble species could be obtained that incorporated folate bound via the spacer to fluorinated organics. These species were shown through imaging studies with phantoms to exhibit promise as ultra contrast agents and hence future work will focus on examining the uptake of these agnets by cells that overexpress the folate receptor. To that end, methodology has been developed to examine the uptake of the conjugates and determine their affinities for the folate receptor in specific cell lines.