期刊
CLINICAL CANCER RESEARCH
卷 24, 期 20, 页码 4976-4987出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1078-0432.CCR-18-0261
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类别
资金
- NIH [R01CA210553, R01CA134659, R01CA199658, P30 CA 016042]
- University of California-Davis Center for Molecular and Genomic Imaging
- University of California Davis Flow Cytometry Shared Resource Laboratory
- NCI [P30 CA093373]
- NIH NCRR [C06-RR12088, S10 OD018223, S10 RR12964, S10 RR 026825]
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 cysdiabody, labeled with Cu-64, to assess the sensitivity of PET imaging of normal and diseased tissue. Experimental Design: Radiolabeling of an anti-CD8 cysdiabody (169cDb) with Cu-64 was developed. The accumulation of Cu-64-169cDb 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 aPD-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), Cu-64-169cDb 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: Cu-64-169cDb 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. (C) 2018 AACR.
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