title: Biodistribution of (125)I-labeled anti-endoglin antibody using SPECT/CT imaging: Impact of in vivo deiodination on tumor accumulation in mice.
abstract: Radiolabeled antibodies directed against endoglin (CD105) are promising tools for imaging and antiangiogenic cancer therapy. To validate iodinated antibodies as reliable tracers, we investigated the influence of the radiolabeling method (direct or indirect) on their in vivo stability.
  
  
  
  Anti-CD105 mAbs were radioiodinated directly using chloramine-T ((125)I-anti-CD105-mAbs) or indirectly using D-KRYRR peptide as a linker ((125)I-KRYRR-anti-CD105-mAbs). The biodistribution was studied in B16 tumor-bearing mice via SPECT/CT imaging.
  
  
  
  Radioiodinated mAbs were stable in vitro. In vivo, thyroid showed the most important increase of uptake after 24h for (125)I-anti-CD105-mAbs (91.9±4.0%ID/ml) versus(125)I-KRYRR-anti-CD105-mAbs (4.4±0.6%ID/ml). Tumor uptake of (125)I-anti-CD105-mAbs (0.9±0.3%ID/ml) was significantly lower than that of (125)I-KRYRR-anti-CD105-mAbs (4.7±0.2%ID/ml).
  
  
  
  An accurate characterization of the in vivo stability of radioiodinated mAbs and the choice of an appropriate method for the radioiodination are required, especially for novel targets. The indirect radioiodination of internalizing anti-CD105 mAbs leads to more stable tracer by decreasing in vivo deiodination and improves the tumor retention of radioiodinated mAbs.
  
  
  
  To date, the only antiangiogenic antibody approved for clinical indications is bevacizumab. There is a need to develop more antibodies that have targets highly expressed on tumor endothelium. CD105 represents a promising marker of angiogenesis, but its therapeutic relevance in cancer needs to be further investigated. In this context, this study suggests the potential use of indirectly iodinated anti-CD105 mAbs for tumor imaging and for therapeutic purposes.
authors.affiliation: Biomedical Magnetic Resonance Research Group (REMA), Louvain Drug Research Institute (LDRI), Université Catholique de Louvain, Avenue Mounier 73, 1200, Brussels, Belgium.
authors.forename: Linda
authors.initials: L
authors.lastname: Karmani
authors.affiliation: Biomedical Magnetic Resonance Research Group (REMA), Louvain Drug Research Institute (LDRI), Université Catholique de Louvain, Avenue Mounier 73, 1200, Brussels, Belgium.
authors.forename: Philippe
authors.initials: P
authors.lastname: Levêque
authors.affiliation: Pharmacology and Therapeutics Unit (FATH), Institute of Experimental and Clinical Research (IREC), Université Catholique de Louvain, Avenue Mounier 53, 1200, Brussels, Belgium.
authors.forename: Caroline
authors.initials: C
authors.lastname: Bouzin
authors.affiliation: Centre for Molecular Imaging, Radiotherapy and Oncology (MIRO), Institute of Experimental and Clinical Research (IREC), Université Catholique de Louvain, Avenue Hippocrate 54, 1200, Brussels, Belgium.
authors.forename: Anne
authors.initials: A
authors.lastname: Bol
authors.affiliation: Unité de Recherche en Biologie Cellulaire (URBC), Namur Research Institute for Life Sciences (NARILIS), University of Namur, Rue de Bruxelles 61, 5000, Namur, Belgium.
authors.forename: Marc
authors.initials: M
authors.lastname: Dieu
authors.affiliation: Centre for Molecular Imaging, Radiotherapy and Oncology (MIRO), Institute of Experimental and Clinical Research (IREC), Université Catholique de Louvain, Avenue Hippocrate 54, 1200, Brussels, Belgium.
authors.forename: Stephan
authors.initials: S
authors.lastname: Walrand
authors.affiliation: Centre for Molecular Imaging, Radiotherapy and Oncology (MIRO), Institute of Experimental and Clinical Research (IREC), Université Catholique de Louvain, Avenue Hippocrate 54, 1200, Brussels, Belgium.
authors.forename: Thierry
authors.initials: T
authors.lastname: Vander Borght
authors.affiliation: Pharmacology and Therapeutics Unit (FATH), Institute of Experimental and Clinical Research (IREC), Université Catholique de Louvain, Avenue Mounier 53, 1200, Brussels, Belgium.
authors.forename: Olivier
authors.initials: O
authors.lastname: Feron
authors.affiliation: Centre for Molecular Imaging, Radiotherapy and Oncology (MIRO), Institute of Experimental and Clinical Research (IREC), Université Catholique de Louvain, Avenue Hippocrate 54, 1200, Brussels, Belgium.
authors.forename: Vincent
authors.initials: V
authors.lastname: Grégoire
authors.affiliation: Namur Research College and Department of Chemistry (NARC), University of Namur, Rue de Bruxelles 61, 5000, Namur, Belgium.
authors.forename: Davide
authors.initials: D
authors.lastname: Bonifazi
authors.affiliation: Unité de Recherche en Biologie Cellulaire (URBC), Namur Research Institute for Life Sciences (NARILIS), University of Namur, Rue de Bruxelles 61, 5000, Namur, Belgium.
authors.forename: Carine
authors.initials: C
authors.lastname: Michiels
authors.affiliation: Research Centre for the Physics of Matter and Radiation (PMR), Namur Research Institute for Life Sciences (NARILIS), University of Namur, Rue de Bruxelles 61, 5000, Namur, Belgium.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Lucas
authors.affiliation: Biomedical Magnetic Resonance Research Group (REMA), Louvain Drug Research Institute (LDRI), Université Catholique de Louvain, Avenue Mounier 73, 1200, Brussels, Belgium. Electronic address: Bernard.Gallez@uclouvain.be.
authors.forename: Bernard
authors.initials: B
authors.lastname: Gallez
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology; D045744:Cell Line, Tumor; D000071063:Endoglin / Q000276:immunology*; D015972:Gene Expression Regulation, Neoplastic; D018796:Immunoconjugates / Q000737:chemistry* / Q000493:pharmacokinetics*; D007457:Iodine Radioisotopes; D007553:Isotope Labeling; D008546:Melanoma, Experimental / Q000000981:diagnostic imaging* / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D051381:Rats; D000072098:Single Photon Emission Computed Tomography Computed Tomography / Q000379:methods*; D014018:Tissue Distribution
chemical_list: D000911:Antibodies, Monoclonal; D000071063:Endoglin; D018796:Immunoconjugates; D007457:Iodine Radioisotopes
keywords: Anti-endoglin antibody; CD105; Deiodination; KRYRR; SPECT/CT; Tumor