2024-03-28T08:47:21Zhttp://repisalud.isciii.es/oai/requestoai:repisalud.isciii.es:20.500.12105/66582022-07-05T07:58:28Zcom_20.500.12105_2174com_20.500.12105_2051com_20.500.12105_2173col_20.500.12105_2175
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.
1555-4309
http://hdl.handle.net/20.500.12105/6658
30224904
10.1155/2018/8382148
1555-4317
Contrast media & molecular imaging
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