CD8+ T-cell density imaging with 64Cu-labeled cys-diabody informs immunotherapy protocols

Jai Woong Seo, Richard Tavaré, Lisa M. Mahakian, Matthew T. Silvestrini, Sarah Tam, Elizabeth S. Ingham, Felix B. Salazar, Alexander D. Borowsky, Anna M. Wu, Katherine W Ferrara

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

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 64Cu, to assess the sensitivity of PET imaging of normal and diseased tissue. Experimental Design: Radiolabeling of an anti-CD8 cysdiabody (169cDb) with 64Cu was developed. The accumulation of 64Cu-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), 64Cu-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: 64Cu-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.

Original languageEnglish (US)
Pages (from-to)4976-4987
Number of pages12
JournalClinical Cancer Research
Volume24
Issue number20
DOIs
StatePublished - Oct 15 2018

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'CD8+ T-cell density imaging with 64Cu-labeled cys-diabody informs immunotherapy protocols'. Together they form a unique fingerprint.

  • Cite this

    Seo, J. W., Tavaré, R., Mahakian, L. M., Silvestrini, M. T., Tam, S., Ingham, E. S., Salazar, F. B., Borowsky, A. D., Wu, A. M., & Ferrara, K. W. (2018). CD8+ T-cell density imaging with 64Cu-labeled cys-diabody informs immunotherapy protocols. Clinical Cancer Research, 24(20), 4976-4987. https://doi.org/10.1158/1078-0432.CCR-18-0261