2026-07-23T17:12:36Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/66582024-11-29T14:24:21Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597

00925njm 22002777a 4500 dc Morcillo, Miguel Ángel author García de Lucas, Ángel author Oteo, Marta author Romero, Eduardo author Magro, Natalia author Ibáñez, Marta author Martínez, Alfonso author Garaulet, Guillermo author Arroyo, Alicia G author Lopez Casas, Pedro Pablo author Hidalgo, Manuel author Mulero, Francisca author Martinez Torrecuadrada, Jorge Luis author 2018 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 different uptake levels. The 89Zr-DFO-LEM2/15 probe showed greater specific 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 89Zr-DFO-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. Contrast Media Mol Imaging. 2018; 2018:8382148. 10.1155/2018/8382148 1555-4317 1555-4309 Contrast media & molecular imaging 30224904 http://hdl.handle.net/20.500.12105/6658 P-ISOTHIOCYANATOBENZYL-DESFERRIOXAMINE TYPE-1 MATRIX-METALLOPROTEINASE IN-VIVO MONOCLONAL-ANTIBODIES BIFUNCTIONAL CHELATE TUMOR-GROWTH INVASION ANGIOGENESIS ZIRCONIUM-89 NHIBITION MT1-MMP as a PET Imaging Biomarker for Pancreas Cancer Management