title: Imaging, Biodistribution, and Dosimetry of Radionuclide-Labeled PD-L1 Antibody in an Immunocompetent Mouse Model of Breast Cancer.
abstract: The programmed cell death ligand 1 (PD-L1) participates in an immune checkpoint system involved in preventing autoimmunity. PD-L1 is expressed on tumor cells, tumor-associated macrophages, and other cells in the tumor microenvironment. Anti-PD-L1 antibodies are active against a variety of cancers, and combined anti-PD-L1 therapy with external beam radiotherapy has been shown to increase therapeutic efficacy. PD-L1 expression status is an important indicator of prognosis and therapy responsiveness, but methods to precisely capture the dynamics of PD-L1 expression in the tumor microenvironment are still limited. In this study, we developed a murine anti-PD-L1 antibody conjugated to the radionuclide Indium-111 ((111)In) for imaging and biodistribution studies in an immune-intact mouse model of breast cancer. The distribution of (111)In-DTPA-anti-PD-L1 in tumors as well as the spleen, liver, thymus, heart, and lungs peaked 72 hours after injection. Coinjection of labeled and 100-fold unlabeled antibody significantly reduced spleen uptake at 24 hours, indicating that an excess of unlabeled antibody effectively blocked PD-L1 sites in the spleen, thus shifting the concentration of (111)In-DTPA-anti-PD-L1 into the blood stream and potentially increasing tumor uptake. Clearance of (111)In-DTPA-anti-PD-L1 from all organs occurred at 144 hours. Moreover, dosimetry calculations revealed that radionuclide-labeled anti-PD-L1 antibody yielded tolerable projected marrow doses, further supporting its use for radiopharmaceutical therapy. Taken together, these studies demonstrate the feasibility of using anti-PD-L1 antibody for radionuclide imaging and radioimmunotherapy and highlight a new opportunity to optimize and monitor the efficacy of immune checkpoint inhibition therapy.
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, School of Medicine, Baltimore, Maryland.
authors.forename: Anders
authors.initials: A
authors.lastname: Josefsson
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, School of Medicine, Baltimore, Maryland.
authors.forename: Jessie R
authors.initials: JR
authors.lastname: Nedrow
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, School of Medicine, Baltimore, Maryland.
authors.forename: Sunju
authors.initials: S
authors.lastname: Park
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, School of Medicine, Baltimore, Maryland.
authors.forename: Sangeeta Ray
authors.initials: SR
authors.lastname: Banerjee
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, School of Medicine, Baltimore, Maryland.
authors.forename: Andrew
authors.initials: A
authors.lastname: Rittenbach
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, School of Medicine, Baltimore, Maryland.
authors.forename: Fabien
authors.initials: F
authors.lastname: Jammes
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, School of Medicine, Baltimore, Maryland.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Tsui
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, School of Medicine, Baltimore, Maryland. gsgouros@jhmi.edu.
authors.forename: George
authors.initials: G
authors.lastname: Sgouros
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D011379:Prognosis; D061026:Programmed Cell Death 1 Receptor / Q000235:genetics* / Q000276:immunology*; D011880:Radiotherapy Planning, Computer-Assisted; D059016:Tumor Microenvironment
chemical_list: D061026:Programmed Cell Death 1 Receptor