Author/Authors :
Angel Morcillo, Miguel Biomedical Applications of Radioisotopes and Pharmacokinetics - Research Centre for Energy - Environment and Technology (CIEMAT) - Madrid, Spain , Garcıa de Lucas, Angel Biomedical Applications of Radioisotopes and Pharmacokinetics - Research Centre for Energy - Environment and Technology (CIEMAT) - Madrid, Spain , Oteo, Marta Biomedical Applications of Radioisotopes and Pharmacokinetics - Research Centre for Energy - Environment and Technology (CIEMAT) - Madrid, Spain , Romero, Eduardo Biomedical Applications of Radioisotopes and Pharmacokinetics - Research Centre for Energy - Environment and Technology (CIEMAT) - Madrid, Spain , Magro, Natalia Biomedical Applications of Radioisotopes and Pharmacokinetics - Research Centre for Energy - Environment and Technology (CIEMAT) - Madrid, Spain , Ibañez, Marta Biomedical Applications of Radioisotopes and Pharmacokinetics - Research Centre for Energy - Environment and Technology (CIEMAT) - Madrid, Spain , Martınez, Alfonso Biomedical Applications of Radioisotopes and Pharmacokinetics - Research Centre for Energy - Environment and Technology (CIEMAT) - Madrid, Spain , Garaulet, Guillermo Molecular Imaging Unit - Spanish National Cancer Research Centre (CNIO) - Madrid, Spain , Arroyo, Alicia G Matrix Metalloproteinases in Angiogenesis and Inflammation Lab - Centro de Investigaciones Biolo´gicas (CIB-CSIC) - Madrid, Spain , Lopez-Casas, Pedro Pablo Gastrointestinal Cancer Clinical Research Unit - Madrid, Spain , Hidalgo, Manuel Gastrointestinal Cancer Clinical Research Unit - Madrid, Spain , Mulero, Francisca Molecular Imaging Unit - Spanish National Cancer Research Centre (CNIO) - Madrid, Spain , Martınez-Torrecuadrada, Jorge Crystallography and Protein Engineering Unit - Madrid, Spain
Abstract :
Pancreatic ductal adenocarcinoma (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 be extremely useful to improve disease diagnosis and
follow-up. MT1-MMP has long been involved in pancreatic cancer, especially in tumour invasion and metastasis. In this study, we
aim to ascertain the suitability of MT1-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 68Ga and with 89Zr. PET imaging with both probes was conducted in patient-derived xenograft (PDX),
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 MT1-MMP
although they did so at difierent uptake levels. The 89Zr-DFO-LEM2/15 probe showed greater specic activity compared to the 68Ga-labelled peptide. The mean value of tumour uptake for the 89Zr-DFO-LEM2/15 probe (5.67 ± 1.11%ID/g, n = 28) was 25–30
times higher than that of the 68Ga-DOTA-AF7p ones. Tumour/blood ratios (1.13 ± 0.51 and 1.44 ± 0.43 at 5 and 7 days of 89ZrDFO-LEM2/15 after injection) were higher than those estimated for 68Ga-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 MT1-MMP by PET imaging is
a promising strategy for PDAC diagnosis and (ii) labelled LEM2/15 antibody is a better candidate than MT1-AF7p for
PDAC detection.
Keywords :
MT1-MMP , PET , Management , PDAC
