MMP-14 as a noninvasive marker for PET and NIRF imaging of glioblastoma multiforme

1033 Background: Glioblastoma multiforme (GBM) is a rapidly proliferating and invasive cancer originating from the glial cells of the brain. GBMs are diffuse, with indistinct tumor margins leading to incomplete surgical resection and subsequent recurrence. Matrix metalloproteinase 14 (MMP-14) is an enzyme that degrades the extracellular matrix. MMP-14 is highly expressed in GBM, and is involved in the invasion of the cancerous cells into the surrounding tissue. The primary treatment for GBM is surgery, with an increasing percentage of the tumor removed correlating to improved survival of the patient. However, current imaging of GBM pre-surgery is difficult to translate during surgery due to shift in the tissue. Combinatorial imaging of MMP-14 pre-surgery with PET, and intra-operatively with near infrared fluorescence (NIRF) would allow for improved surgical resection of the tumor. We have developed peptides to bind MMP-14, which are suitable for both PET and NIRF imaging. Methods: Several peptide constructs were developed and used for imaging in mice bearing orthotopic patient derived xenograft GBMs. Construct 1 exhibited binding affinity to MMP-14, construct 2 was a substrate for MMP-14, and construct 3 was a combination of 1 and 2. Constructs 1 and 3 were labeled with 68Ga or 64Cu and used for PET imaging. Constructs 2 and 3 were fluorescent and were used for NIRF imaging. Results: Immunohistochemistry showed the presence of MMP-14 in the tumor areas, which was co-localized with fluorescence signal from probes 2 and 3. Radiolabeled probes 1 and 3 showed accumulation in the tumor, which could be significantly reduced with the addition of non-labeled blocking peptides (p