A Polymer-Based Magnetic Resonance Tracer for Visualization of Solid Tumors by (13)C Spectroscopic Imaging

Morphological imaging precedes lesion-specific visualization in magnetic resonance imaging (MRI) because of the superior ability of this technique to depict tissue morphology with excellent spatial and temporal resolutions. To achieve lesion-specific visualization of tumors by MRI, we investigated the availability of a novel polymer-based tracer. Although the (13)C nucleus is a candidate for a detection nucleus because of its low background signal in the body, the low magnetic resonance sensitivity of the nucleus needs to be resolved before developing a (13)C-based tracer. In order to overcome this problem, we enriched polyethylene glycol (PEG), a biocompatible polymer, with (13)C atoms. (13)C-PEG40,000 ((13)C-PEG with an average molecular weight of 40 kDa) emitted a single (13)C signal with a high signal-to-noise ratio due to its ability to maintain signal sharpness, as was confirmed by in vivo investigation, and displayed a chemical shift sufficiently distinct from that of endogenous fat. (13)C-PEG40,000 intravenously injected into mice showed long retention in circulation, leading to its effective accumulation in tumors reflecting the well-known phenomenon that macromolecules accumulate in tumors because of leaky tumor capillaries. These properties of (13)C-PEG40,000 allowed visualization of tumors in mice by (13)C spectroscopic imaging. These findings suggest that a technique based on (13)C-PEG is a promising strategy for tumor detection.