A Multimodal Contrast Agent for Preoperative MR Imaging and Intraoperative Tumor Margin Delineation

Abstract

We have constructed a multimodal contrast agent suitable for near-infrared, NIR, fluorescent imaging as well as magnetic resonance imaging, MRI. This class of agents may be useful for preoperative tumor localization and tumor functional evaluation and for intraoperative delineation of tumor margins. We have covalently attached dyes of the cyanine family to a previously described polymeric contrast agent, Gd-DTPA-polylysine, of an extended, uncoiled conformation. The dual modality agent is as effective in imaging tumors by MRI as the parent compound provided that the dye loading on the polymer is such that it does not eliminate all the available free-lysine groups on the parent Gd-DTPA-polylysine polymers. NIR fluorescence from preclinical subcutaneous and orthotopic mammary gland tumors could be detected with a signal to background ratio of as high as 4.5 at 12 hours post agent injection at a dye dose of 125 nmole/kg. For intraoperative delineation of tumor margins, a wide-field illumination camera system was devised giving high signal to background NIR fluorescent images of surgically exposed orthotopic mammary gland tumors. Histologic microscopy confirmed the location of the dual modality agent at the boundary of the tumor with a margin distance of about 0.3 mm from labeled tumor cells.