title: Molecular Magnetic Resonance Imaging of Tumors with a PTPµ Targeted Contrast Agent.
abstract: 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 PTPµ 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 PTPµ 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.
authors.affiliation: Department of Molecular Biology and Microbiology, School of Medicine, Case Western Reserve University, Cleveland, OH.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Burden-Gulley
authors.forename: Zhuxian
authors.initials: Z
authors.lastname: Zhou
authors.forename: Sonya El
authors.initials: SE
authors.lastname: Craig
authors.forename: Zheng-Rong
authors.initials: ZR
authors.lastname: Lu
authors.forename: Susann M
authors.initials: SM
authors.lastname: Brady-Kalnay