title: Immuno-PET Imaging of Engineered Human T Cells in Tumors.
abstract: Sensitive in vivo imaging technologies applicable to the clinical setting are still lacking for adoptive T-cell-based immunotherapies, an important gap to fill if mechanisms of tumor rejection or escape are to be understood. Here, we propose a highly sensitive imaging technology to track human TCR-transgenic T cells in vivo by directly targeting the murinized constant TCR beta domain (TCRmu) with a zirconium-89 ((89)Zr)-labeled anti-TCRmu-F(ab')2 fragment. Binding of the labeled or unlabeled F(ab')2 fragment did not impair functionality of transgenic T cells in vitro and in vivo Using a murine xenograft model of human myeloid sarcoma, we monitored by Immuno-PET imaging human central memory T cells (TCM), which were transgenic for a myeloid peroxidase (MPO)-specific TCR. Diverse T-cell distribution patterns were detected by PET/CT imaging, depending on the tumor size and rejection phase. Results were confirmed by IHC and semiquantitative evaluation of T-cell infiltration within the tumor corresponding to the PET/CT images. Overall, these findings offer a preclinical proof of concept for an imaging approach that is readily tractable for clinical translation. Cancer Res; 76(14); 4113-23. ©2016 AACR.
authors.affiliation: Medizinische Klinik III, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Mall
authors.affiliation: Nuklearmedizinische Klinik und Poliklinik, Technische Universität München, Munich, Germany.
authors.forename: Nahid
authors.initials: N
authors.lastname: Yusufi
authors.affiliation: Medizinische Klinik III, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Ricarda
authors.initials: R
authors.lastname: Wagner
authors.affiliation: Medizinische Klinik III, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Richard
authors.initials: R
authors.lastname: Klar
authors.affiliation: Medizinische Klinik III, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Henrique
authors.initials: H
authors.lastname: Bianchi
authors.affiliation: Institut für Allgemeine Pathologie und Pathologische Anatomie, Technische Universität München, Munich, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Steiger
authors.affiliation: Institut für Allgemeine Pathologie und Pathologische Anatomie, Technische Universität München, Munich, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Straub
authors.affiliation: Medizinische Klinik III, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Audehm
authors.affiliation: Nuklearmedizinische Klinik und Poliklinik, Technische Universität München, Munich, Germany.
authors.forename: Iina
authors.initials: I
authors.lastname: Laitinen
authors.affiliation: Research Unit Analytical Pathology, Helmholtz Zentrum München, Munich, Germany.
authors.forename: Michaela
authors.initials: M
authors.lastname: Aichler
authors.affiliation: Medizinische Klinik III, Klinikum rechts der Isar, Technische Universität München, Munich, Germany. German Cancer Consortium (DKTK), Munich, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Peschel
authors.affiliation: Nuklearmedizinische Klinik und Poliklinik, Technische Universität München, Munich, Germany.
authors.forename: Sibylle
authors.initials: S
authors.lastname: Ziegler
authors.affiliation: Nuklearmedizinische Klinik und Poliklinik, Technische Universität München, Munich, Germany.
authors.forename: Mona
authors.initials: M
authors.lastname: Mustafa
authors.affiliation: Nuklearmedizinische Klinik und Poliklinik, Technische Universität München, Munich, Germany. German Cancer Consortium (DKTK), Munich, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Schwaiger
authors.affiliation: Nuklearmedizinische Klinik und Poliklinik, Technische Universität München, Munich, Germany.
authors.forename: Calogero
authors.initials: C
authors.lastname: D'Alessandria
authors.affiliation: Medizinische Klinik III, Klinikum rechts der Isar, Technische Universität München, Munich, Germany. German Cancer Consortium (DKTK), Munich, Germany. Clinical Cooperation Group Antigen Specific T-Cell Therapy, Helmholtz Zentrum München, Munich, Germany. angela.krackhardt@tum.de.
authors.forename: Angela M
authors.initials: AM
authors.lastname: Krackhardt
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D018014:Gene Transfer Techniques; D006801:Humans; D007156:Immunologic Memory; D016219:Immunotherapy, Adoptive; D051379:Mice; D009369:Neoplasms / Q000000981:diagnostic imaging / Q000276:immunology*; D000072078:Positron Emission Tomography Computed Tomography / Q000379:methods*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D011948:Receptors, Antigen, T-Cell