PET of Adoptively Transferred Chimeric Antigen Receptor T Cells with ^sup 89^Zr-Oxine
Chimeric antigen receptor (CAR) T cell therapy is a promising clinical approach for reducing tumor progression and prolonging patient survival. However, improvements in both the safety and the potency of CAR T cell therapy demand quantitative imaging techniques to determine the distribution of cells...
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Published in | The Journal of nuclear medicine (1978) Vol. 59; no. 10; p. 1531 |
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Main Authors | , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
New York
Society of Nuclear Medicine
01.10.2018
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Subjects | |
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Abstract | Chimeric antigen receptor (CAR) T cell therapy is a promising clinical approach for reducing tumor progression and prolonging patient survival. However, improvements in both the safety and the potency of CAR T cell therapy demand quantitative imaging techniques to determine the distribution of cells after adoptive transfer. The purpose of this study was to optimize £sup£89¥sup¥Zr-oxine labeling of CAR T cells and evaluate PET as a platform for imaging adoptively transferred CAR T cells. Methods: CAR T cells were labeled with 0–1.4 MBq of £sup£89¥sup¥Zr-oxine per 10£sup£6¥sup¥ cells and assessed for radioactivity retention, viability, and functionality. In vivo trafficking of £sup£89¥sup¥Zr-oxine–labeled CAR T cells was evaluated in 2 murine xenograft tumor models: glioblastoma brain tumors with intracranially delivered IL13Rα2-targeted CAR T cells, and subcutaneous prostate tumors with intravenously delivered prostate stem cell antigen (PSCA)–targeted CAR T cells. Results: CAR T cells were efficiently labeled (75%) and retained more than 60% of the £sup£89¥sup¥Zr over 6 d. In vitro cytokine production, migration, and tumor cytotoxicity, as well as in vivo antitumor activity, were not significantly reduced when labeled with 70 kBq/10£sup£6¥sup¥ cells. IL13Rα2-CAR T cells delivered intraventricularly were detectable by PET for at least 6 d throughout the central nervous system and within intracranial tumors. When intravenously administered, PSCA-CAR T cells also showed tumor tropism, with a 9-fold greater tumor-to-muscle ratio than for CAR-negative T cells. Conclusion: £sup£89¥sup¥Zr-oxine can be used for labeling and imaging CAR T cells while maintaining cell viability and function. On the basis of these studies, we conclude that £sup£89¥sup¥Zr-oxine is a clinically translatable platform for real-time assessment of cell therapies. |
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AbstractList | Chimeric antigen receptor (CAR) T cell therapy is a promising clinical approach for reducing tumor progression and prolonging patient survival. However, improvements in both the safety and the potency of CAR T cell therapy demand quantitative imaging techniques to determine the distribution of cells after adoptive transfer. The purpose of this study was to optimize £sup£89¥sup¥Zr-oxine labeling of CAR T cells and evaluate PET as a platform for imaging adoptively transferred CAR T cells. Methods: CAR T cells were labeled with 0–1.4 MBq of £sup£89¥sup¥Zr-oxine per 10£sup£6¥sup¥ cells and assessed for radioactivity retention, viability, and functionality. In vivo trafficking of £sup£89¥sup¥Zr-oxine–labeled CAR T cells was evaluated in 2 murine xenograft tumor models: glioblastoma brain tumors with intracranially delivered IL13Rα2-targeted CAR T cells, and subcutaneous prostate tumors with intravenously delivered prostate stem cell antigen (PSCA)–targeted CAR T cells. Results: CAR T cells were efficiently labeled (75%) and retained more than 60% of the £sup£89¥sup¥Zr over 6 d. In vitro cytokine production, migration, and tumor cytotoxicity, as well as in vivo antitumor activity, were not significantly reduced when labeled with 70 kBq/10£sup£6¥sup¥ cells. IL13Rα2-CAR T cells delivered intraventricularly were detectable by PET for at least 6 d throughout the central nervous system and within intracranial tumors. When intravenously administered, PSCA-CAR T cells also showed tumor tropism, with a 9-fold greater tumor-to-muscle ratio than for CAR-negative T cells. Conclusion: £sup£89¥sup¥Zr-oxine can be used for labeling and imaging CAR T cells while maintaining cell viability and function. On the basis of these studies, we conclude that £sup£89¥sup¥Zr-oxine is a clinically translatable platform for real-time assessment of cell therapies. |
Author | Yang, Xin Poku, Erasmus Weist, Michael R Aguilar, Brenda Gerdts, Ethan Shively, John E Starr, Renate Chea, Junie Miles, Joshua K man, Stephen J Brown, Christine E Colcher, David Priceman, Saul J |
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Snippet | Chimeric antigen receptor (CAR) T cell therapy is a promising clinical approach for reducing tumor progression and prolonging patient survival. However,... |
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SubjectTerms | Adoptive transfer Animal models Anticancer properties Antitumor activity Biocompatibility Brain Brain cancer Brain tumors Central nervous system Chimeric antigen receptors Cytotoxicity Glioblastoma Imaging Imaging techniques Interleukin 1 Labelling Lymphocytes Lymphocytes T Muscles Neuroimaging Positron emission Positron emission tomography Positrons Prostate Prostate cancer Radioactivity Stem cells T cell receptors Therapy Tomography Toxicity Tropism Tumors Xenografts Xenotransplantation Zirconium Zirconium oxides |
Title | PET of Adoptively Transferred Chimeric Antigen Receptor T Cells with ^sup 89^Zr-Oxine |
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