MT1-MMP as a PET Imaging Biomarker for Pancreas Cancer Management

Pancreatic ductal adenocareinoma (PDAC) continues to be one of the deadliest cancers for which optimal diagnostic tools are still greatly needed. Identification of PDAC-specific molecular markers would he extremely useful to improve disease diagnosis and follow-up. MTI-MMP has long been involved in pancreatic cancer, especially in tumour invasion and metastasis. In this study, we aim to ascertain the suitability of MTI-MMP as a biomarker for positron emission tomography (PET) imaging. Two probes were assessed and compared for this purpose, an MT1-MMP-specific binding peptide (MT1-AF7p) and a specific antibody (LEM2/15), labelled, respectively, with Ga-68 and with Zr-89. PET imaging with both probes was conducted in patient-derived xenograft subcutaneous and orthotopic, PDAC mouse models, and in a cancer cell line (CAPAN-2)-derived xenograft (CDX) model. Both radiolabelled tracers were successful in identifying, by means of PET imaging techniques, tumour tissues expressing MTI-MMP although they did so at different uptake levels. The Zr-89-DFO-LEM2/15 probe showed greater specific activity compared to the Ga-68-labelled peptide. The mean value of tumour uptake for the Zr-89-DFO-LEM2/15 probe (5.67 +/- 1.11%ID/g, n = 28) was 25-30 times higher than that of the Ga-68-DOTA-AF7p ones. Tumour/blood ratios (1.13 +/- 0.51 and 1.44 +/- 0.43 at 5 and 7 days of Zr-89-DFO-LEM2/15 after injection) were higher than those estimated for Ga-68-DOTA-AF7p probes (of approximately tumour/blood ratio = 0.5 at 90 min after injection). Our findings strongly point out that (i) the in vivo detection of MTI-MMP by PET imaging is a promising strategy for PDAC diagnosis and (ii) labelled LEM2/15 antibody is a better candidate than MTI-AF7p for PDAC detection.