title: MMP-13 In-Vivo Molecular Imaging Reveals Early Expression in Lung Adenocarcinoma.
abstract: BACKGROUND
  Several matrix metalloproteinases (MMPs) are overexpressed in lung cancer and may serve as potential targets for the development of bioactivable probes for molecular imaging.
  
  
  OBJECTIVE
  To characterize and monitor the activity of MMPs during the progression of lung adenocarcinoma.
  
  
  METHODS
  K-rasLSL-G12D mice were imaged serially during the development of adenocarcinomas using fluorescence molecular tomography (FMT) and a probe specific for MMP-2, -3, -9 and -13. Lung tumors were identified using FMT and MRI co-registration, and the probe concentration in each tumor was assessed at each time-point. The expression of Mmp2, -3, -9, -13 was quantified by qRT-PCR using RNA isolated from microdissected tumor cells. Immunohistochemical staining of overexpressed MMPs in animals was assessed on human lung tumors.
  
  
  RESULTS
  In mice, 7 adenomas and 5 adenocarcinomas showed an increase in fluorescent signal on successive FMT scans, starting between weeks 4 and 8. qRT-PCR assays revealed significant overexpression of only Mmp-13 in mice lung tumors. In human tumors, a high MMP-13 immunostaining index was found in tumor cells from invasive lesions (24/27), but in none of the non-invasive (0/4) (p=0.001).
  
  
  CONCLUSIONS
  MMP-13 is detected in early pulmonary invasive adenocarcinomas and may be a potential target for molecular imaging of lung cancer.
authors.affiliation: Cancer Prevention and Control Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania, United States of America; Laboratoire Quant.I.F - LITIS, EA 4108, Rouen University, Rouen, France; Clinique Pneumologique & CIC INSERM U1404, Rouen University Hospital, Rouen, France.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Salaün
authors.affiliation: Cancer Prevention and Control Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania, United States of America.
authors.forename: Jing
authors.initials: J
authors.lastname: Peng
authors.affiliation: Biological Imaging Facility, Fox Chase Cancer Center, Philadelphia, Pennsylvania, United States of America.
authors.forename: Harvey H
authors.initials: HH
authors.lastname: Hensley
authors.affiliation: Cancer Prevention and Control Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania, United States of America.
authors.forename: Navid
authors.initials: N
authors.lastname: Roder
authors.affiliation: Department of Pathology, Fox Chase Cancer Center, Philadelphia, Pennsylvania, United States of America.
authors.forename: Douglas B
authors.initials: DB
authors.lastname: Flieder
authors.affiliation: Department of Pathology, Rouen University Hospital, Rouen, France.
authors.forename: Solène
authors.initials: S
authors.lastname: Houlle-Crépin
authors.affiliation: Department of Pathology, Rouen University Hospital, Rouen, France.
authors.forename: Olivia
authors.initials: O
authors.lastname: Abramovici-Roels
authors.affiliation: Department of Pathology, Rouen University Hospital, Rouen, France.
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Sabourin
authors.affiliation: Laboratoire Quant.I.F - LITIS, EA 4108, Rouen University, Rouen, France; Clinique Pneumologique & CIC INSERM U1404, Rouen University Hospital, Rouen, France.
authors.forename: Luc
authors.initials: L
authors.lastname: Thiberville
authors.affiliation: Cancer Prevention and Control Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania, United States of America.
authors.forename: Margie L
authors.initials: ML
authors.lastname: Clapper
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology*; D000236:Adenoma / Q000378:metabolism / Q000473:pathology; D000818:Animals; D006801:Humans; D007150:Immunohistochemistry; D008168:Lung / Q000378:metabolism; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D053509:Matrix Metalloproteinase 13 / Q000235:genetics / Q000378:metabolism*; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D061848:Optical Imaging; D012334:RNA, Neoplasm / Q000032:analysis; D060888:Real-Time Polymerase Chain Reaction; D014057:Tomography, X-Ray Computed; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D012334:RNA, Neoplasm; D053509:Matrix Metalloproteinase 13; D020782:Matrix Metalloproteinases; D018631:ras Proteins