Molecular Magnetic Resonance Imaging of Tumors with a PTPμ Targeted Contrast Agent

Molecular magnetic resonance imaging (MRI) of tumors improves the specificity of MRI by using targeted probes conjugated to contrast-generating metals. The limitation of this approach is in the identification of a target molecule present in sufficient concentration for visualization and the development of a labeling reagent that can penetrate tumor tissue with the fast kinetics required for use in a clinical setting. The receptor protein tyrosine phosphatase PTP mu is a transmembrane protein that is continuously proteolyzed in the tumor microenvironment to generate a high concentration of extracellular fragment that can be recognized by the SBK2 probe. We conjugated the SBK2 peptide to a gadolinium chelate [SBK2-Tris-(Gd-DOTA)(3)] to test whether the SBK2 probe could be developed as an MR molecular imaging probe. When intravenously injected into mice bearing flank tumors of human glioma cells, SBK2-Tris-(Gd-DOTA)(3) labeled the tumors within 5 minutes with a high level of contrast for up to 2 hours post-injection. The contrast enhancement of SBK2-Tris-(Gd-DOTA)(3) was significantly higher than that observed with a current MRI macrocyclic gadolinium chelate (Gadoteridol, ProHance) alone or a scrambled control. These results demonstrate that SBK2-Tris-(Gd-DOTA)(3) labeling of the PTP mu extracellular fragment is a more specific MR molecular imaging probe than ProHance or a scrambled control. Consequently, the SBK2 probe may be more useful than the current gold standard reagent for MRI to identify tumors and to co-register tumor borders during surgical resection.