title: Selective in vivo imaging of syngeneic, spontaneous, and xenograft tumors using a novel tumor cell-specific hsp70 peptide-based probe.
abstract: Although in vivo targeting of tumors using fluorescently labeled probes has greatly gained in importance over the last few years, most of the clinically applied reagents lack tumor cell specificity. Our novel tumor cell-penetrating peptide-based probe (TPP) recognizes an epitope of Hsp70 that is exclusively present on the cell surface of a broad variety of human and mouse tumors and metastases, but not on normal tissues. Because of the rapid turnover rate of membrane Hsp70, fluorescently labeled TPP is continuously internalized into syngeneic, spontaneous, chemically/genetically induced and xenograft tumors following intravenous administration, thereby enabling site-specific labeling of primary tumors and metastases. In contrast with the commercially available nonpeptide small molecule αvβ3-integrin antagonist IntegriSense, TPP exhibits a significantly higher tumor-to-background contrast and stronger tumor-specific signal intensity in all tested tumor models. Moreover, in contrast with IntegriSense, TPP reliably differentiates between tumor cells and cells of the tumor microenvironment, such as tumor-associated macrophages and fibroblasts, which were found to be membrane-Hsp70 negative. Therefore, TPP provides a useful tool for multimodal imaging of tumors and metastases that might help to improve our understanding of tumorigenesis and allow the establishment of improved diagnostic procedures and more accurate therapeutic monitoring. TPP might also be a promising platform for tumor-specific drug delivery and other Hsp70-based targeted therapies.
authors.affiliation: Department of Radiation Oncology, Klinikum rechts der Isar, TU München and CCG - "Innate Immunity in Tumor Biology", Helmholtz Zentrum München (HMGU), Munich, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Stangl
authors.affiliation: Institute for Tumor Biology and Experimental Therapy, Georg-Speyer-Haus, Frankfurt/Main, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Varga
authors.affiliation: Department of Radiation Oncology, Klinikum rechts der Isar, TU München and CCG - "Innate Immunity in Tumor Biology", Helmholtz Zentrum München (HMGU), Munich, Germany.
authors.forename: Bianca
authors.initials: B
authors.lastname: Freysoldt
authors.affiliation: Department of Medicine II, Klinikum rechts der Isar, TU München, Munich, Germany.
authors.forename: Marija
authors.initials: M
authors.lastname: Trajkovic-Arsic
authors.affiliation: Department of Medicine II, Klinikum rechts der Isar, TU München, Munich, Germany.
authors.forename: Jens T
authors.initials: JT
authors.lastname: Siveke
authors.affiliation: Institute for Tumor Biology and Experimental Therapy, Georg-Speyer-Haus, Frankfurt/Main, Germany.
authors.forename: Florian R
authors.initials: FR
authors.lastname: Greten
authors.affiliation: Institute of Biological and Medical Imaging, Helmholtz Zentrum München (HMGU), Munich, Germany.
authors.forename: Vasilis
authors.initials: V
authors.lastname: Ntziachristos
authors.affiliation: Department of Radiation Oncology, Klinikum rechts der Isar, TU München and CCG - "Innate Immunity in Tumor Biology", Helmholtz Zentrum München (HMGU), Munich, Germany. gabriele.multhoff@lrz.tu-muenchen.de.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Multhoff
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000378:metabolism; D045744:Cell Line, Tumor; D057846:Cell-Penetrating Peptides / Q000378:metabolism*; D003952:Diagnostic Imaging / Q000379:methods; D005260:Female; D005456:Fluorescent Dyes / Q000378:metabolism*; D045325:HCT116 Cells; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D006367:HeLa Cells; D064593:Heterografts / Q000378:metabolism; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D061986:MCF-7 Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D064847:Multimodal Imaging / Q000379:methods; D059016:Tumor Microenvironment / Q000502:physiology
chemical_list: D057846:Cell-Penetrating Peptides; D005456:Fluorescent Dyes; D018840:HSP70 Heat-Shock Proteins; D039302:Integrin alphaVbeta3