title: Potential of activatable FAP-targeting immunoliposomes in intraoperative imaging of spontaneous metastases.
abstract: Despite intensive research and medical advances met, metastatic disease remains the most common cause of death in cancer patients. This results from late diagnosis, poor therapeutic response and undetected micrometastases and tumor margins during surgery. One approach to overcome these challenges involves fluorescence imaging, which exploits the properties of fluorescent probes for diagnostic detection of molecular structures at the onset of transformation and for intraoperative detection of metastases and tumor margins in real time. Considering these benefits, many contrast agents suitable for fluorescence imaging have been reported. However, most reports only demonstrate the detection of primary tumors and not the detection of metastases or their application in models of image-guided surgery. In this work, we demonstrate the influence of fibroblast activation protein (FAP) on the metastatic potential of fibrosarcoma cells and elucidate the efficacy of activatable FAP-targeting immunoliposomes (FAP-IL) for image-guided detection of the spontaneous metastases in mice models. Furthermore, we characterized the biodistribution and cellular localization of the liposomal fluorescent components in mice organs and traced their excretion over time in urine and feces. Taken together, activatable FAP-IL enhances intraoperative imaging of metastases. Their high accumulation in metastases, subsequent localization in the bile canaliculi and liver kupffer cells and suitable excretion in feces substantiates their potency as contrast agents for intraoperative imaging.
authors.affiliation: Dept. of Experimental Radiology, Institute of Diagnostic and Interventional Radiology, Jena University Hospital - Friedrich Schiller University Jena, Erlanger Allee 101, 07747 Jena, Germany. Electronic address: felista.tansi@med.uni-jena.de.
authors.forename: Felista L
authors.initials: FL
authors.lastname: Tansi
authors.affiliation: Department of Pharmaceutical Technology, Friedrich-Schiller-University Jena, Lessingstrasse 8, 07743 Jena, Germany. Electronic address: ronny.rueger@web.de.
authors.forename: Ronny
authors.initials: R
authors.lastname: Rüger
authors.affiliation: Dept. of Experimental Radiology, Institute of Diagnostic and Interventional Radiology, Jena University Hospital - Friedrich Schiller University Jena, Erlanger Allee 101, 07747 Jena, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Böhm
authors.affiliation: Institute of Cell Biology and Immunology, University Stuttgart, Allmandring 31, 70569 Stuttgart, Germany.
authors.forename: Roland E
authors.initials: RE
authors.lastname: Kontermann
authors.affiliation: Dept. of Experimental Radiology, Institute of Diagnostic and Interventional Radiology, Jena University Hospital - Friedrich Schiller University Jena, Erlanger Allee 101, 07747 Jena, Germany.
authors.forename: Ulf K
authors.initials: UK
authors.lastname: Teichgraeber
authors.affiliation: Department of Pharmaceutical Technology, Friedrich-Schiller-University Jena, Lessingstrasse 8, 07743 Jena, Germany.
authors.forename: Alfred
authors.initials: A
authors.lastname: Fahr
authors.affiliation: Dept. of Experimental Radiology, Institute of Diagnostic and Interventional Radiology, Jena University Hospital - Friedrich Schiller University Jena, Erlanger Allee 101, 07747 Jena, Germany. Electronic address: ingrid.hilger@med.uni-jena.de.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Hilger
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D010450:Endopeptidases; D005260:Female; D005354:Fibrosarcoma / Q000378:metabolism / Q000473:pathology*; D018093:Gelatinases / Q000378:metabolism*; D006801:Humans; D008081:Liposomes / Q000378:metabolism* / Q000493:pharmacokinetics*; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D057054:Molecular Imaging / Q000379:methods*; D009362:Neoplasm Metastasis / Q000175:diagnosis* / Q000473:pathology; D012697:Serine Endopeptidases / Q000378:metabolism*; D000099167:Fibroblast Activation Protein Alpha
chemical_list: D010450:Endopeptidases; D018093:Gelatinases; D008081:Liposomes; D008565:Membrane Proteins; D012697:Serine Endopeptidases; D000099167:Fibroblast Activation Protein Alpha
keywords: FAP; Fibrosarcoma; Fluorescence-quenching; Liposomes; Molecular imaging; Spontaneous metastasis