CD8 + T-Cell Density Imaging with 64 Cu-Labeled Cys-Diabody Informs Immunotherapy Protocols.

Autor:	Seo JW; Department of Biomedical Engineering, University of California, Davis, Davis, California., Tavaré R; Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California., Mahakian LM; Department of Biomedical Engineering, University of California, Davis, Davis, California., Silvestrini MT; Department of Biomedical Engineering, University of California, Davis, Davis, California., Tam S; Department of Biomedical Engineering, University of California, Davis, Davis, California., Ingham ES; Department of Biomedical Engineering, University of California, Davis, Davis, California., Salazar FB; Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California., Borowsky AD; Center for Comparative Medicine, University of California, Davis, Davis, California., Wu AM; Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California., Ferrara KW; Department of Biomedical Engineering, University of California, Davis, Davis, California. kwferrara@ucdavis.edu.
Jazyk:	angličtina
Zdroj:	Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2018 Oct 15; Vol. 24 (20), pp. 4976-4987. Date of Electronic Publication: 2018 Jul 02.
DOI:	10.1158/1078-0432.CCR-18-0261
Abstrakt:	Purpose: Noninvasive and quantitative tracking of CD8 + T cells by PET has emerged as a potential technique to gauge response to immunotherapy. We apply an anti-CD8 cys-diabody, labeled with 64 Cu, to assess the sensitivity of PET imaging of normal and diseased tissue. Experimental Design: Radiolabeling of an anti-CD8 cys-diabody (169cDb) with 64 Cu was developed. The accumulation of 64 Cu-169cDb was evaluated with PET/CT imaging (0, 5, and 24 hours) and biodistribution (24 hours) in wild-type mouse strains ( n = 8/group studied with imaging and IHC or flow cytometry) after intravenous administration. Tumor-infiltrating CD8 + T cells in tumor-bearing mice treated with CpG and αPD-1 were quantified and mapped ( n = 6-8/group studied with imaging and IHC or flow cytometry). Results: We demonstrate the ability of immunoPET to detect small differences in CD8 + T-cell distribution between mouse strains and across lymphoid tissues, including the intestinal tract of normal mice. In FVB mice bearing a syngeneic HER2 -driven model of mammary adenocarcinoma (NDL), 64 Cu-169cDb PET imaging accurately visualized and quantified changes in tumor-infiltrating CD8 + T cells in response to immunotherapy. A reduction in the circulation time of the imaging probe followed the development of treatment-related liver and splenic hypertrophy and provided an indication of off-target effects associated with immunotherapy protocols. Conclusions: 64 Cu-169cDb imaging can spatially map the distribution of CD8 + T cells in normal organs and tumors. ImmunoPET imaging of tumor-infiltrating cytotoxic CD8 + T cells detected changes in T-cell density resulting from adjuvant and checkpoint immunotherapy protocols in our preclinical evaluation. Clin Cancer Res; 24(20); 4976-87. ©2018 AACR . (©2018 American Association for Cancer Research.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu