Cargando…
In vivo imaging of CD8(+) T cells in metastatic cancer patients: first clinical experience with simultaneous [(89)Zr]Zr-Df-IAB22M2C PET/MRI
Aim/Introduction: Despite the spectacular success of immune checkpoint inhibitor therapy (ICT) in patients with metastatic cancer, only a limited proportion of patients benefit from ICT. CD8(+) cytotoxic T cells are important gatekeepers for the therapeutic response to ICT and are able to recognize...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Ivyspring International Publisher
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10196830/ https://www.ncbi.nlm.nih.gov/pubmed/37215571 http://dx.doi.org/10.7150/thno.79976 |
_version_ | 1785044428627378176 |
---|---|
author | Schwenck, Johannes Sonanini, Dominik Seyfried, Dominik Ehrlichmann, Walter Kienzle, Gabriele Reischl, Gerald Krezer, Pascal Wilson, Ian Korn, Ron Gonzalez-Menendez, Irene Quintanilla-Martinez, Leticia Seith, Ferdinand Forschner, Andrea Eigentler, Thomas Zender, Lars Röcken, Martin Pichler, Bernd J Flatz, Lukas Kneilling, Manfred la Fougere, Christian |
author_facet | Schwenck, Johannes Sonanini, Dominik Seyfried, Dominik Ehrlichmann, Walter Kienzle, Gabriele Reischl, Gerald Krezer, Pascal Wilson, Ian Korn, Ron Gonzalez-Menendez, Irene Quintanilla-Martinez, Leticia Seith, Ferdinand Forschner, Andrea Eigentler, Thomas Zender, Lars Röcken, Martin Pichler, Bernd J Flatz, Lukas Kneilling, Manfred la Fougere, Christian |
author_sort | Schwenck, Johannes |
collection | PubMed |
description | Aim/Introduction: Despite the spectacular success of immune checkpoint inhibitor therapy (ICT) in patients with metastatic cancer, only a limited proportion of patients benefit from ICT. CD8(+) cytotoxic T cells are important gatekeepers for the therapeutic response to ICT and are able to recognize MHC class I-dependent tumor antigens and destroy tumor cells. The radiolabeled minibody [(89)Zr]Zr-Df-IAB22M2C has a high affinity for human CD8(+) T cells and was successfully tested in a phase I study. Here, we aimed to gain the first clinical PET/MRI experience with the noninvasive assessment of the CD8(+) T-cell distribution in cancer patients by in vivo [(89)Zr]Zr-Df-IAB22M2C with a distinct focus of identifying potential signatures of successful ICT. Material and Methods: We investigated 8 patients with metastasized cancers undergoing ICT. Radiolabeling of Df-IAB22M2C with Zr-89 was performed according to Good Manufacturing Practice. Multiparametric PET/MRI was acquired 24 h after injection of 74.2±17.9 MBq [(89)Zr]Zr-Df-IAB22M2C. We analyzed [(89)Zr]Zr-Df-IAB22M2C uptake within the metastases and within primary and secondary lymphatic organs. Results: [(89)Zr]Zr-Df-IAB22M2C injection was tolerated well without noticeable side effects. The CD8 PET/MRI data acquisitions 24 hours post-administration of [(89)Zr]Zr-Df-IAB22M2C revealed good image quality with a relatively low background signal due to only low unspecific tissue uptake and marginal blood pool retention. Only two metastatic lesions showed markedly increased tracer uptake in our cohort of patients. Furthermore, we observed high interpatient variability in [(89)Zr]Zr-Df-IAB22M2C uptake within the primary and secondary lymphoid organs. Four out of five ICT patients exhibited rather high [(89)Zr]Zr-Df-IAB22M2C uptake in the bone marrow. Two of these four patients as well as two other patients yielded pronounced [(89)Zr]Zr-Df-IAB22M2C uptake within nonmetastatic lymph nodes. Interestingly, cancer progression in ICT patients was associated with a relatively low [(89)Zr]Zr-Df-IAB22M2C uptake in the spleen compared to the liver in 4 out of the 6 patients. Lymph nodes with enhanced [(89)Zr]Zr-Df-IAB22M2C uptake revealed significantly reduced apparent diffusion coefficient (ADC) values in diffusion weighted MRI. Conclusion: Our first clinical experiences revealed the feasibility of [(89)Zr]Zr-Df-IAB22M2C PET/MRI in assessing potential immune-related changes in metastases and primary and secondary lymphatic organs. According to our results, we hypothesize that alterations in [(89)Zr]Zr-Df-IAB22M2C uptake in primary and secondary lymphoid organs might be associated with the response to ICT. |
format | Online Article Text |
id | pubmed-10196830 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Ivyspring International Publisher |
record_format | MEDLINE/PubMed |
spelling | pubmed-101968302023-05-20 In vivo imaging of CD8(+) T cells in metastatic cancer patients: first clinical experience with simultaneous [(89)Zr]Zr-Df-IAB22M2C PET/MRI Schwenck, Johannes Sonanini, Dominik Seyfried, Dominik Ehrlichmann, Walter Kienzle, Gabriele Reischl, Gerald Krezer, Pascal Wilson, Ian Korn, Ron Gonzalez-Menendez, Irene Quintanilla-Martinez, Leticia Seith, Ferdinand Forschner, Andrea Eigentler, Thomas Zender, Lars Röcken, Martin Pichler, Bernd J Flatz, Lukas Kneilling, Manfred la Fougere, Christian Theranostics Research Paper Aim/Introduction: Despite the spectacular success of immune checkpoint inhibitor therapy (ICT) in patients with metastatic cancer, only a limited proportion of patients benefit from ICT. CD8(+) cytotoxic T cells are important gatekeepers for the therapeutic response to ICT and are able to recognize MHC class I-dependent tumor antigens and destroy tumor cells. The radiolabeled minibody [(89)Zr]Zr-Df-IAB22M2C has a high affinity for human CD8(+) T cells and was successfully tested in a phase I study. Here, we aimed to gain the first clinical PET/MRI experience with the noninvasive assessment of the CD8(+) T-cell distribution in cancer patients by in vivo [(89)Zr]Zr-Df-IAB22M2C with a distinct focus of identifying potential signatures of successful ICT. Material and Methods: We investigated 8 patients with metastasized cancers undergoing ICT. Radiolabeling of Df-IAB22M2C with Zr-89 was performed according to Good Manufacturing Practice. Multiparametric PET/MRI was acquired 24 h after injection of 74.2±17.9 MBq [(89)Zr]Zr-Df-IAB22M2C. We analyzed [(89)Zr]Zr-Df-IAB22M2C uptake within the metastases and within primary and secondary lymphatic organs. Results: [(89)Zr]Zr-Df-IAB22M2C injection was tolerated well without noticeable side effects. The CD8 PET/MRI data acquisitions 24 hours post-administration of [(89)Zr]Zr-Df-IAB22M2C revealed good image quality with a relatively low background signal due to only low unspecific tissue uptake and marginal blood pool retention. Only two metastatic lesions showed markedly increased tracer uptake in our cohort of patients. Furthermore, we observed high interpatient variability in [(89)Zr]Zr-Df-IAB22M2C uptake within the primary and secondary lymphoid organs. Four out of five ICT patients exhibited rather high [(89)Zr]Zr-Df-IAB22M2C uptake in the bone marrow. Two of these four patients as well as two other patients yielded pronounced [(89)Zr]Zr-Df-IAB22M2C uptake within nonmetastatic lymph nodes. Interestingly, cancer progression in ICT patients was associated with a relatively low [(89)Zr]Zr-Df-IAB22M2C uptake in the spleen compared to the liver in 4 out of the 6 patients. Lymph nodes with enhanced [(89)Zr]Zr-Df-IAB22M2C uptake revealed significantly reduced apparent diffusion coefficient (ADC) values in diffusion weighted MRI. Conclusion: Our first clinical experiences revealed the feasibility of [(89)Zr]Zr-Df-IAB22M2C PET/MRI in assessing potential immune-related changes in metastases and primary and secondary lymphatic organs. According to our results, we hypothesize that alterations in [(89)Zr]Zr-Df-IAB22M2C uptake in primary and secondary lymphoid organs might be associated with the response to ICT. Ivyspring International Publisher 2023-04-17 /pmc/articles/PMC10196830/ /pubmed/37215571 http://dx.doi.org/10.7150/thno.79976 Text en © The author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions. |
spellingShingle | Research Paper Schwenck, Johannes Sonanini, Dominik Seyfried, Dominik Ehrlichmann, Walter Kienzle, Gabriele Reischl, Gerald Krezer, Pascal Wilson, Ian Korn, Ron Gonzalez-Menendez, Irene Quintanilla-Martinez, Leticia Seith, Ferdinand Forschner, Andrea Eigentler, Thomas Zender, Lars Röcken, Martin Pichler, Bernd J Flatz, Lukas Kneilling, Manfred la Fougere, Christian In vivo imaging of CD8(+) T cells in metastatic cancer patients: first clinical experience with simultaneous [(89)Zr]Zr-Df-IAB22M2C PET/MRI |
title | In vivo imaging of CD8(+) T cells in metastatic cancer patients: first clinical experience with simultaneous [(89)Zr]Zr-Df-IAB22M2C PET/MRI |
title_full | In vivo imaging of CD8(+) T cells in metastatic cancer patients: first clinical experience with simultaneous [(89)Zr]Zr-Df-IAB22M2C PET/MRI |
title_fullStr | In vivo imaging of CD8(+) T cells in metastatic cancer patients: first clinical experience with simultaneous [(89)Zr]Zr-Df-IAB22M2C PET/MRI |
title_full_unstemmed | In vivo imaging of CD8(+) T cells in metastatic cancer patients: first clinical experience with simultaneous [(89)Zr]Zr-Df-IAB22M2C PET/MRI |
title_short | In vivo imaging of CD8(+) T cells in metastatic cancer patients: first clinical experience with simultaneous [(89)Zr]Zr-Df-IAB22M2C PET/MRI |
title_sort | in vivo imaging of cd8(+) t cells in metastatic cancer patients: first clinical experience with simultaneous [(89)zr]zr-df-iab22m2c pet/mri |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10196830/ https://www.ncbi.nlm.nih.gov/pubmed/37215571 http://dx.doi.org/10.7150/thno.79976 |
work_keys_str_mv | AT schwenckjohannes invivoimagingofcd8tcellsinmetastaticcancerpatientsfirstclinicalexperiencewithsimultaneous89zrzrdfiab22m2cpetmri AT sonaninidominik invivoimagingofcd8tcellsinmetastaticcancerpatientsfirstclinicalexperiencewithsimultaneous89zrzrdfiab22m2cpetmri AT seyfrieddominik invivoimagingofcd8tcellsinmetastaticcancerpatientsfirstclinicalexperiencewithsimultaneous89zrzrdfiab22m2cpetmri AT ehrlichmannwalter invivoimagingofcd8tcellsinmetastaticcancerpatientsfirstclinicalexperiencewithsimultaneous89zrzrdfiab22m2cpetmri AT kienzlegabriele invivoimagingofcd8tcellsinmetastaticcancerpatientsfirstclinicalexperiencewithsimultaneous89zrzrdfiab22m2cpetmri AT reischlgerald invivoimagingofcd8tcellsinmetastaticcancerpatientsfirstclinicalexperiencewithsimultaneous89zrzrdfiab22m2cpetmri AT krezerpascal invivoimagingofcd8tcellsinmetastaticcancerpatientsfirstclinicalexperiencewithsimultaneous89zrzrdfiab22m2cpetmri AT wilsonian invivoimagingofcd8tcellsinmetastaticcancerpatientsfirstclinicalexperiencewithsimultaneous89zrzrdfiab22m2cpetmri AT kornron invivoimagingofcd8tcellsinmetastaticcancerpatientsfirstclinicalexperiencewithsimultaneous89zrzrdfiab22m2cpetmri AT gonzalezmenendezirene invivoimagingofcd8tcellsinmetastaticcancerpatientsfirstclinicalexperiencewithsimultaneous89zrzrdfiab22m2cpetmri AT quintanillamartinezleticia invivoimagingofcd8tcellsinmetastaticcancerpatientsfirstclinicalexperiencewithsimultaneous89zrzrdfiab22m2cpetmri AT seithferdinand invivoimagingofcd8tcellsinmetastaticcancerpatientsfirstclinicalexperiencewithsimultaneous89zrzrdfiab22m2cpetmri AT forschnerandrea invivoimagingofcd8tcellsinmetastaticcancerpatientsfirstclinicalexperiencewithsimultaneous89zrzrdfiab22m2cpetmri AT eigentlerthomas invivoimagingofcd8tcellsinmetastaticcancerpatientsfirstclinicalexperiencewithsimultaneous89zrzrdfiab22m2cpetmri AT zenderlars invivoimagingofcd8tcellsinmetastaticcancerpatientsfirstclinicalexperiencewithsimultaneous89zrzrdfiab22m2cpetmri AT rockenmartin invivoimagingofcd8tcellsinmetastaticcancerpatientsfirstclinicalexperiencewithsimultaneous89zrzrdfiab22m2cpetmri AT pichlerberndj invivoimagingofcd8tcellsinmetastaticcancerpatientsfirstclinicalexperiencewithsimultaneous89zrzrdfiab22m2cpetmri AT flatzlukas invivoimagingofcd8tcellsinmetastaticcancerpatientsfirstclinicalexperiencewithsimultaneous89zrzrdfiab22m2cpetmri AT kneillingmanfred invivoimagingofcd8tcellsinmetastaticcancerpatientsfirstclinicalexperiencewithsimultaneous89zrzrdfiab22m2cpetmri AT lafougerechristian invivoimagingofcd8tcellsinmetastaticcancerpatientsfirstclinicalexperiencewithsimultaneous89zrzrdfiab22m2cpetmri |