TY - JOUR T1 - Antigen-Dependent Inducible T-Cell Reporter System for PET Imaging of Breast Cancer and Glioblastoma JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 137 LP - 144 DO - 10.2967/jnumed.122.264284 VL - 64 IS - 1 AU - Jaehoon Shin AU - Matthew F.L. Parker AU - Iowis Zhu AU - Aryn Alanizi AU - Carlos I. Rodriguez AU - Raymond Liu AU - Payal B. Watchmaker AU - Mausam Kalita AU - Joseph Blecha AU - Justin Luu AU - Brian Wright AU - Suzanne E. Lapi AU - Robert R. Flavell AU - Hideho Okada AU - Thea D. Tlsty AU - Kole T. Roybal AU - David M. Wilson Y1 - 2023/01/01 UR - http://jnm.snmjournals.org/content/64/1/137.abstract N2 - For the past several decades, chimeric antigen receptor T-cell therapies have shown promise in the treatment of cancers. These treatments would greatly benefit from companion imaging biomarkers to follow the trafficking of T cells in vivo. Methods: Using synthetic biology, we engineered T cells with a chimeric receptor synthetic intramembrane proteolysis receptor (SNIPR) that induces overexpression of an exogenous reporter gene cassette on recognition of specific tumor markers. We then applied a SNIPR-based PET reporter system to 2 cancer-relevant antigens, human epidermal growth factor receptor 2 (HER2) and epidermal growth factor receptor variant III (EGFRvIII), commonly expressed in breast and glial tumors, respectively. Results: Antigen-specific reporter induction of the SNIPR PET T cells was confirmed in vitro using green fluorescent protein fluorescence, luciferase luminescence, and the HSV-TK PET reporter with 9-(4-18F-fluoro-3-[hydroxymethyl]butyl)guanine ([18F]FHBG). T cells associated with their target antigens were successfully imaged using PET in dual-xenograft HER2+/HER2− and EGFRvIII+/EGFRvIII− animal models, with more than 10-fold higher [18F]FHBG signals seen in antigen-expressing tumors versus the corresponding controls. Conclusion: The main innovation found in this work was PET detection of T cells via specific antigen-induced signals, in contrast to reporter systems relying on constitutive gene expression. ER -