title: An Effective Immuno-PET Imaging Method to Monitor CD8-Dependent Responses to Immunotherapy.
abstract: The rapidly advancing field of cancer immunotherapy is currently limited by the scarcity of noninvasive and quantitative technologies capable of monitoring the presence and abundance of CD8(+) T cells and other immune cell subsets. In this study, we describe the generation of (89)Zr-desferrioxamine-labeled anti-CD8 cys-diabody ((89)Zr-malDFO-169 cDb) for noninvasive immuno-PET tracking of endogenous CD8(+) T cells. We demonstrate that anti-CD8 immuno-PET is a sensitive tool for detecting changes in systemic and tumor-infiltrating CD8 expression in preclinical syngeneic tumor immunotherapy models including antigen-specific adoptive T-cell transfer, agonistic antibody therapy (anti-CD137/4-1BB), and checkpoint blockade antibody therapy (anti-PD-L1). The ability of anti-CD8 immuno-PET to provide whole body information regarding therapy-induced alterations of this dynamic T-cell population provides new opportunities to evaluate antitumor immune responses of immunotherapies currently being evaluated in the clinic.
authors.affiliation: Crump Institute for Molecular Imaging, University of California Los Angeles, Los Angeles, California. Department of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, California. rtavare@mednet.ucla.edu awu@mednet.ucla.edu.
authors.forename: Richard
authors.initials: R
authors.lastname: Tavaré
authors.affiliation: Department of Medicine, Division of Hematology-Oncology, University of California Los Angeles, Los Angeles, California.
authors.forename: Helena
authors.initials: H
authors.lastname: Escuin-Ordinas
authors.affiliation: Department of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, California.
authors.forename: Stephen
authors.initials: S
authors.lastname: Mok
authors.affiliation: Department of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, California.
authors.forename: Melissa N
authors.initials: MN
authors.lastname: McCracken
authors.affiliation: Crump Institute for Molecular Imaging, University of California Los Angeles, Los Angeles, California. Department of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, California.
authors.forename: Kirstin A
authors.initials: KA
authors.lastname: Zettlitz
authors.affiliation: Crump Institute for Molecular Imaging, University of California Los Angeles, Los Angeles, California. Department of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, California.
authors.forename: Felix B
authors.initials: FB
authors.lastname: Salazar
authors.affiliation: Department of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, California. Howard Hughes Medical Institute, University of California Los Angeles, Los Angeles, California. Department of Microbiology, Immunology and Molecular Genetics, University of California Los Angeles, Los Angeles, California. Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California Los Angeles, Los Angeles, California.
authors.forename: Owen N
authors.initials: ON
authors.lastname: Witte
authors.affiliation: Department of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, California. Department of Medicine, Division of Hematology-Oncology, University of California Los Angeles, Los Angeles, California. Jonsson Comprehensive Cancer Center, University of California Los Angeles, Los Angeles, California. Surgery, Division of Surgical Oncology, University of California Los Angeles, Los Angeles, California. Institute for Molecular Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California.
authors.forename: Antoni
authors.initials: A
authors.lastname: Ribas
authors.affiliation: Crump Institute for Molecular Imaging, University of California Los Angeles, Los Angeles, California. Department of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, California. Jonsson Comprehensive Cancer Center, University of California Los Angeles, Los Angeles, California. rtavare@mednet.ucla.edu awu@mednet.ucla.edu.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Wu
mesh_terms: D000818:Animals; D018033:Antibodies, Bispecific; D016827:CD8 Antigens; D018414:CD8-Positive T-Lymphocytes / Q000000981:diagnostic imaging* / Q000276:immunology*; D003110:Colonic Neoplasms / Q000000981:diagnostic imaging* / Q000276:immunology / Q000628:therapy*; D003676:Deferoxamine / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology; D004195:Disease Models, Animal; D006801:Humans; D018796:Immunoconjugates / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology; D016219:Immunotherapy, Adoptive / Q000379:methods*; D016246:Lymphocytes, Tumor-Infiltrating / Q000000981:diagnostic imaging / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D049268:Positron-Emission Tomography / Q000379:methods*; D011868:Radioisotopes / Q000008:administration & dosage* / Q000737:chemistry; D019275:Radiopharmaceuticals / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology; D015040:Zirconium / Q000008:administration & dosage* / Q000737:chemistry
chemical_list: D018033:Antibodies, Bispecific; D016827:CD8 Antigens; D018796:Immunoconjugates; D011868:Radioisotopes; D019275:Radiopharmaceuticals; D015040:Zirconium; D003676:Deferoxamine