title: Investigations on the usefulness of CEACAMs as potential imaging targets for molecular imaging purposes.
abstract: Members of the carcinoembryonic antigen cell adhesion molecules (CEACAMs) family are the prototype of tumour markers. Classically they are used as serum markers, however, CEACAMs could serve as targets for molecular imaging as well.In order to test the anti CEACAM monoclonal antibody T84.1 for imaging purposes, CEACAM expression was analysed using this antibody. Twelve human cancer cell lines from different entities were screened for their CEACAM expression using qPCR, Western Blot and FACS analysis. In addition, CEACAM expression was analyzed in primary tumour xenografts of these cells. Nine of 12 tumour cell lines expressed CEACAM mRNA and protein when grown in vitro. Pancreatic and colon cancer cell lines showed the highest expression levels with good correlation of mRNA and protein level. However, when grown in vivo, the CEACAM expression was generally downregulated except for the melanoma cell lines. As the CEACAM expression showed pronounced expression in FemX-1 primary tumours, this model system was used for further experiments. As the accessibility of the antibody after i.v. application is critical for its use in molecular imaging, the binding of the T84.1 monoclonal antibody was assessed after i.v. injection into SCID mice harbouring a FemX-1 primary tumour. When applied i.v., the CEACAM specific T84.1 antibody bound to tumour cells in the vicinity of blood vessels. This binding pattern was particularly pronounced in the periphery of the tumour xenograft, however, some antibody binding was also observed in the central areas of the tumour around blood vessels. Still, a general penetration of the tumour by i.v. application of the anti CEACAM antibody could not be achieved despite homogenous CEACAM expression of all melanoma cells when analysed in tissue sections. This lack of penetration is probably due to the increased interstitial fluid pressure in tumours caused by the absence of functional lymphatic vessels.
authors.affiliation: Institute of Anatomy and Experimental Morphology, University Hospital Hamburg-Eppendorf, Hamburg, Germany. ma.heine@uke.uni-hamburg.de
authors.forename: Markus
authors.initials: M
authors.lastname: Heine
authors.forename: Peter
authors.initials: P
authors.lastname: Nollau
authors.forename: Christoph
authors.initials: C
authors.lastname: Masslo
authors.forename: Peter
authors.initials: P
authors.lastname: Nielsen
authors.forename: Barbara
authors.initials: B
authors.lastname: Freund
authors.forename: Oliver T
authors.initials: OT
authors.lastname: Bruns
authors.forename: Rudolph
authors.initials: R
authors.lastname: Reimer
authors.forename: Heinrich
authors.initials: H
authors.lastname: Hohenberg
authors.forename: Kersten
authors.initials: K
authors.lastname: Peldschus
authors.forename: Harald
authors.initials: H
authors.lastname: Ittrich
authors.forename: Udo
authors.initials: U
authors.lastname: Schumacher
mesh_terms: D000418:Albumins / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D015415:Biomarkers / Q000378:metabolism; D018938:Caco-2 Cells; D002272:Carcinoembryonic Antigen / Q000737:chemistry / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D045744:Cell Line, Tumor; D005070:Evans Blue / Q000494:pharmacology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D042601:Lymphatic Vessels / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D057054:Molecular Imaging / Q000379:methods; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D000418:Albumins; D015703:Antigens, CD; D015415:Biomarkers; C069847:CD66 antigens; D002272:Carcinoembryonic Antigen; D015815:Cell Adhesion Molecules; D012333:RNA, Messenger; D005070:Evans Blue