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MT1-MMP as a PET imaging biomarker for pancreas cancer management

AuthorsMorcillo, Miguel Ángel; García de Lucas, Ángel; Oteo, Marta; Romero, Eduardo; Magro, Natalia; Ibáñez, Marta; Martínez, Alfonso; Garaulet, Guillermo; Arroyo, Alicia G. ; López-Casas, Pedro P. ; Hidalgo, Manuel ; Mulero, Francisca; Martínez-Torrecuadrada, Jorge Luis
Issue Date26-Aug-2018
PublisherHindawi Publishing Corporation
CitationContrast Media & Molecular Imaging 8382148 (2018)
AbstractPancreatic 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, a MT1-MMP-specific binding peptide, MT1-AF7p, and a specific antibody, LEM2/15, labelled respectively with 68Ga 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-DFOLEM2/ 15 probe showed greater specific activity compared to the 68Ga-labelled peptide. The mean value of tumour uptake for the 89Zr-DFO-LEM 2/15 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-LEM 2/15 post-injection were higher than those estimated for 68Ga-DOTAAF7p probes (of approximately tumour/blood ratio=0.5 at 90 min post-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.
Description13 p.-5 fig.
Publisher version (URL)https://doi.org/10.1155/2018/8382148
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