PET of Adoptively Transferred Chimeric Antigen Receptor T Cells with ^sup 89^Zr-Oxine

• Published in: The Journal of nuclear medicine (1978) Vol. 59; no. 10; p. 1531
• Main Authors: Miles, Joshua K, Poku, Erasmus, Gerdts, Ethan, Yang, Xin, Priceman, Saul J, man, Stephen J, Colcher, David, Brown, Christine E, Shively, John E, Weist, Michael R, Aguilar, Brenda, Starr, Renate, Chea, Junie
• Format: Journal Article
• Language: English
• Published: New York Society of Nuclear Medicine 01.10.2018
• Subjects: 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
• ISSN: 0161-5505; 1535-5667

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.