Visualization of varying MT1-MMP expression with a phage display derived bicyclic peptide using µPET imaging

Ziel/Aim:

Tumor-associated membrane type 1 matrix metalloproteinase (MT1-MMP) is reported to play an important role in extracellular matrix remodeling, resulting in metastatic dissemination, and to be associated with poor prognosis in a variety of cancers (e.g. non-small cell lung cancer, gastric and breast cancer). This study investigates the potential of a novel phage display derived bicyclic peptide to distinguish between different MT1-MMP-expression levels using small animal PET imaging.

Methodik/Methods:

Comparative µPET imaging was performed 1h after injection of 300 pmol (approx. 15 MBq) Ga-68-labeled bicyclic peptide in balb/c nu/nu mice bearing xenografts of HT1080 (high MT1-MMP expression), DU-145 (medium MT1-MMP expression) or LNCaP (no MT1-MMP expression). Tumor cryosections were collected after µPET imaging and analyzed by autoradiography. IHC was performed on cryosections of a control group of mice using an anti-MT1-MMP IRDye800CW conjugated IgG and NIR-detection.

Ergebnisse/Results:

Comparative µPET studies resulted in a robust association between bicyclic peptide uptake and MT1-MMP expression levels in the tumor xenografts: The highest uptake of the Ga-68-labeled bicyclic peptide was determined in HT1080 tumors, whereby the DU-145 and LNCaP tumors showed medium and no uptake, respectively. Autoradiography and IHC studies confirmed the expression levels as determined by µPET imaging.

Schlussfolgerungen/Conclusions:

The present study demonstrates that in vivo imaging of MT1-MMP expression levels is feasible. Thus, the presented bicyclic peptide represents a highly innovative and promising tool for tumor imaging with PET, which could assist the aim to tailor therapeutic strategies according to the propensity of a tumor to progress, invade and disseminate.