PT  - JOURNAL ARTICLE
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
TI  - Antigen-Dependent Inducible T-Cell Reporter System for PET Imaging of Breast Cancer and Glioblastoma
AID  - 10.2967/jnumed.122.264284
DP  - 2023 Jan 01
TA  - Journal of Nuclear Medicine
PG  - 137--144
VI  - 64
IP  - 1
4099  - http://jnm.snmjournals.org/content/64/1/137.short
4100  - http://jnm.snmjournals.org/content/64/1/137.full
SO  - J Nucl Med2023 Jan 01; 64
AB  - 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.