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Tumor-infiltrating CD8+ T cells and programmed death-1 (PD1) levels are critical indicators for tumor immunophenotyping and therapeutic decision-making. Noninvasive optical imaging in the second near infrared window (NIR-II) is particularly well-suited for investigating the biological processes within tumors in live mammals, thanks to its deep-tissue penetration and superior spatiotemporal resolution. However, in vivo NIR-II imaging has primarily been restricted to a single probe at a time. Methods: Herein, we developed a two-plex NIR-II molecular imaging method utilizing the non-overlapping fluorescence emission of indocyanine green (ICG) in the NIR-IIa window (1000-1200 nm) and PbS/CdS core-shell quantum dots (QDs) in the NIR-IIb window (1500-1700 nm). By integrating PD1 aptamer-labeled ICG (ICG-Apt-PD1, targeting PD1) and CD8 aptamer-labeled QDs (QDs@Apt-CD8, targeting CD8+ T cells), our two-plex NIR-II molecular imaging enabled simultaneous and noninvasive monitoring of the number of CD8+ T cells and PD1 levels in tumors. Results: QDs@Apt-CD8 demonstrated the excellent ability for in vivo imaging of tumor infiltrating CD8+ T cells, owing to its strong NIR-IIb luminescence and the high selectivity and specificity. This two-plex in vivo molecular imaging allowed for dynamic monitoring for PD1 levels and the number of CD8+ T cells in tumors. We observed the heterogeneous bio-distributions of PD1 and CD8+ T cells across different tumor types and revealed the tumor immunophenotypes. Moreover, our findings indicated that the low PD1 and high CD8+ T cells levels in tumors predicted a better anti-tumor effect. Conclusions: Such in vivo noninvasive NIR-II molecular imaging would complement ex vivo biopsy-based diagnostic techniques, and it could contribute to developing an in vivo tumor immune-scoring algorithm to offer a more precise prediction for immunotherapeutic response. © The author(s).
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Theranostics
ISSN: 1838-7640
Year: 2025
Issue: 10
Volume: 15
Page: 4481-4494
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JCR@2023
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ESI Highly Cited Papers on the List: 0 Unfold All
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30 Days PV: 1
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