| Autor: |
De Groof, Timo W.M., Lauwers, Yoline, De Pauw, Tessa, Saxena, Mohit, Vincke, Cécile, Van Craenenbroeck, Jolien, Chapon, Catherine, Le Grand, Roger, Raes, Geert, Naninck, Thibaut, Van Ginderachter, Jo A., Devoogdt, Nick |
| Předmět: |
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| Zdroj: |
European Journal of Nuclear Medicine & Molecular Imaging; Dec2024, Vol. 52 Issue 1, p193-207, 15p |
| Abstrakt: |
Purpose: While immunotherapy has revolutionized the oncology field, variations in therapy responsiveness limit the broad applicability of these therapies. Diagnostic imaging of immune cell, and specifically CD8+ T cell, dynamics could allow early patient stratification and result in improved therapy efficacy and safety. In this study, we report the development of a nanobody-based immunotracer for non-invasive SPECT and PET imaging of human CD8+ T-cell dynamics. Methods: Nanobodies targeting human CD8β were generated by llama immunizations and subsequent biopanning. The lead anti-human CD8β nanobody was characterized on binding, specificity, stability and toxicity. The lead nanobody was labeled with technetium-99m, gallium-68 and copper-64 for non-invasive imaging of human T-cell lymphomas and CD8+ T cells in human CD8 transgenic mice and non-human primates by SPECT/CT or PET/CT. Repeated imaging of CD8+ T cells in MC38 tumor-bearing mice allowed visualization of CD8+ T-cell dynamics. Results: The nanobody-based immunotracer showed high affinity and specific binding to human CD8 without unwanted immune activation. CD8+ T cells were non-invasively visualized by SPECT and PET imaging in naïve and tumor-bearing mice and in naïve non-human primates with high sensitivity. The nanobody-based immunotracer showed enhanced specificity for CD8+ T cells and/or faster in vivo pharmacokinetics compared to previous human CD8-targeting immunotracers, allowing us to follow human CD8+ T-cell dynamics already at early timepoints. Conclusion: This study describes the development of a more specific human CD8+ T-cell-targeting immunotracer, allowing follow-up of immunotherapy responses by non-invasive imaging of human CD8+ T-cell dynamics. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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