Noninvasive imaging of CD4(+) T cells in humanized mice Journal Article
| Authors: | Nagle, V. L.; Hertz, C. A. J.; Henry, K. E.; Graham, M. S.; Campos, C.; Pillarsetty, N.; Schietinger, A.; Mellinghoff, I. K.; Lewis, J. S. |
| Article Title: | Noninvasive imaging of CD4(+) T cells in humanized mice |
| Abstract: | Antibody-based PET (immunoPET) with radiotracers that recognize specific cells of the immune system provides an opportunity to monitor immune cell trafficking at the organismal scale. We previously reported the visualization of human CD8þ T cells, including CD8þ tumor-infiltrating lymphocytes (TIL), in mice using a humanized CD8-targeted minibody. Given the important role of CD4þ T cells in adaptive immune responses of health and disease including infections, tumors, and autoimmunity, we explored immunoPET using an anti-human-CD4 minibody. We assessed the ability of [64Cu]Cu-NOTA-IAB41 to bind to various CD4þ T-cell subsets in vitro. We also determined the effect of the CD4-targeted minibody on CD4þ T-cell abundance, proliferation, and activation state in vitro. We subsequently evaluated the ability of the radiotracer to visualize CD4þ T cells in T-cell rich organs and orthotopic brain tumors in vivo. For the latter, we injected the [64Cu]Cu-NOTA-IAB41 radiotracer into humanized mice that harbored intracranial patient-derived glioblastoma (GBM) xenografts and performed in vivo PET, ex vivo autoradiography, and anti-CD4 IHC on serial brain sections. [64Cu]Cu-NOTA-IAB41 specifically detects human CD4þ T cells without impacting their abundance, proliferation, and activation. In humanized mice, [64Cu]Cu-NOTA-IAB41 can visualize various peripheral tissues in addition to orthotopically implanted GBM tumors. [64Cu]Cu-NOTA-IAB41 is able to visualize human CD4þ T cells in humanized mice and can provide noninvasive quantification of CD4þ T-cell distribution on the organismal scale. 2022 American Association for Cancer Research |
| Keywords: | positron emission tomography; mouse; animal; animals; mice; cell line, tumor; cd4+ t lymphocyte; cd4-positive t-lymphocytes; tumor cell line; positron-emission tomography; copper; copper radioisotopes; procedures; humans; human; copper-64 |
| Journal Title: | Molecular Cancer Therapeutics |
| Volume: | 21 |
| Issue: | 4 |
| ISSN: | 1535-7163 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2022-04-01 |
| Start Page: | 658 |
| End Page: | 666 |
| Language: | English |
| DOI: | 10.1158/1535-7163.Mct-21-0888 |
| PUBMED: | 35131877 |
| PROVIDER: | scopus |
| PMCID: | PMC8983497 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 2 May 2022 -- Source: Scopus |
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271Mellinghoff -
133Pillarsetty -
460Lewis -
37Campos -
42Schietinger -
17Henry -
22Graham -
8Nagle -
8Hertz
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