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

authors

  • Morcillo Alonso, Miguel Ángel
  • GARCIA DE LUCAS, ANGEL
  • Oteo Vives, Marta
  • Romero Sanz, Eduardo
  • Magro Calvo, Natalia
  • Ibáñez Moragues, Marta
  • Martínez Ortega, Alfonso
  • Garaulet Pérez, Guillermo
  • García Arroyo, Alicia
  • López Casas, Pedro Pablo
  • Hidalgo, Manuel
  • Mulero, Francisca
  • Martínez Torrecuadrada, Jorge Luis

publication date

  • August 2018

start page

  • 1

end page

  • 13

volume

  • 2018

International Standard Serial Number (ISSN)

  • 1555-4309

Electronic International Standard Serial Number (EISSN)

  • 1555-4317

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 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.

subjects

  • Biology and Biomedicine
  • Medicine

keywords

  • pet; pancreas cancer