TY - JOUR T1 - PET of Adoptively Transferred Chimeric Antigen Receptor T Cells with <sup>89</sup>Zr-Oxine JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 1531 LP - 1537 DO - 10.2967/jnumed.117.206714 VL - 59 IS - 10 AU - Michael R. Weist AU - Renate Starr AU - Brenda Aguilar AU - Junie Chea AU - Joshua K. Miles AU - Erasmus Poku AU - Ethan Gerdts AU - Xin Yang AU - Saul J. Priceman AU - Stephen J. Forman AU - David Colcher AU - Christine E. Brown AU - John E. Shively Y1 - 2018/10/01 UR - http://jnm.snmjournals.org/content/59/10/1531.abstract N2 - 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 89Zr-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 89Zr-oxine per 106 cells and assessed for radioactivity retention, viability, and functionality. In vivo trafficking of 89Zr-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 89Zr 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/106 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: 89Zr-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 89Zr-oxine is a clinically translatable platform for real-time assessment of cell therapies. ER -