An Effective Immuno-PET Imaging Method to Monitor CD8-Dependent Responses to Immunotherapy

Richard Tavaré; Helena Escuin-Ordinas; Stephen Mok; Melissa N McCracken; Kirstin A Zettlitz; Felix B Salazar; Owen N Witte; Antoni Ribas; Anna M Wu

doi:10.1158/0008-5472.CAN-15-1707

An Effective Immuno-PET Imaging Method to Monitor CD8-Dependent Responses to Immunotherapy

Cancer Res. 2016 Jan 1;76(1):73-82. doi: 10.1158/0008-5472.CAN-15-1707. Epub 2015 Nov 16.

Authors

Richard Tavaré¹, Helena Escuin-Ordinas², Stephen Mok³, Melissa N McCracken³, Kirstin A Zettlitz⁴, Felix B Salazar⁴, Owen N Witte⁵, Antoni Ribas⁶, Anna M Wu⁷

Affiliations

¹ 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.
² Department of Medicine, Division of Hematology-Oncology, University of California Los Angeles, Los Angeles, California.
³ Department of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, California.
⁴ 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.
⁵ 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.
⁶ 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.
⁷ 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.

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antibodies, Bispecific
CD8 Antigens
CD8-Positive T-Lymphocytes / diagnostic imaging*
CD8-Positive T-Lymphocytes / immunology*
Colonic Neoplasms / diagnostic imaging*
Colonic Neoplasms / immunology
Colonic Neoplasms / therapy*
Deferoxamine / administration & dosage
Deferoxamine / chemistry
Deferoxamine / immunology
Disease Models, Animal
Humans
Immunoconjugates / administration & dosage
Immunoconjugates / chemistry
Immunoconjugates / immunology
Immunotherapy, Adoptive / methods*
Lymphocytes, Tumor-Infiltrating / diagnostic imaging
Lymphocytes, Tumor-Infiltrating / immunology
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Positron-Emission Tomography / methods*
Radioisotopes / administration & dosage*
Radioisotopes / chemistry
Radiopharmaceuticals / administration & dosage*
Radiopharmaceuticals / chemistry
Radiopharmaceuticals / immunology
Zirconium / administration & dosage*
Zirconium / chemistry

Substances

Antibodies, Bispecific
CD8 Antigens
Immunoconjugates
Radioisotopes
Radiopharmaceuticals
Zirconium
Deferoxamine

Abstract

Publication types

MeSH terms

Substances

Grants and funding