Dual PET/Fluorescence Imaging of Glioma with an MMP-14-Activatable Peptide Probe
[Technical Report, Annual Report]
University of Alabama at Birmingham
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The purpose of the project is to develop and test, in preclinical models, a sensitive, specific imaging peptide probe to distinguish GBM tissue from healthy tissue. The novel imaging probe targets a cell-surface marker, matrix metalloproteinase14 MMP-14 that is expressed to a much greater degree in GBM cells than in healthy cells. Upon binding to MMP-14, a dual modality fluorescent tag is activated. This tag is detectable by positron emission tomography PET for pre-operative tumor assessment, and by near infrared fluorescence NIRF imaging for real-time surgical guidance in distinguishing tumor cells from healthy cells. Results from the project indicate that GBM cells with MMP-14 activity showed activation and retention of NIRF signal from the cleaved peptide probes. Resected mouse brains with patient derived xenograft PDX GBM tumors showed tumor-to-background NIRF ratios of 7.6-11.1 at 4 h after i.v. injection of the peptides. PET images showed localization of activity in orthotopic PDX tumors after i.v. injection of radiolabeled peptide probes uptake of the radiolabeled probes in tumors was significantly reduced p0.05 by blocking with the non-labeled peptide. PET and NIRF signals correlated linearly in the orthotopic PDX tumors. Immunohistochemistry showed co-localization of MMP-14 expression and NIRF signal in the resected tumors.
- Medicine and Medical Research