title: Longitudinal PET imaging demonstrates biphasic CAR T cell responses in survivors.
abstract: Clinical monitoring of adoptive T cell transfer (ACT) utilizes serial blood analyses to discern T cell activity. While useful, these data are 1-dimensional and lack spatiotemporal information related to treatment efficacy or toxicity. We utilized a human genetic reporter, somatostatin receptor 2 (SSTR2), and PET, to quantitatively and longitudinally visualize whole-body T cell distribution and antitumor dynamics using a clinically approved radiotracer. Initial evaluations determined that SSTR2-expressing T cells were detectable at low densities with high sensitivity and specificity. SSTR2-based PET was applied to ACT of chimeric antigen receptor (CAR) T cells targeting intercellular adhesion molecule-1, which is overexpressed in anaplastic thyroid tumors. Timely CAR T cell infusions resulted in survival of tumor-bearing mice, while later infusions led to uniform death. Real-time PET imaging revealed biphasic T cell expansion and contraction at tumor sites among survivors, with peak tumor burden preceding peak T cell burden by several days. In contrast, nonsurvivors displayed unrelenting increases in tumor and T cell burden, indicating that tumor growth was outpacing T cell killing. Thus, longitudinal PET imaging of SSTR2-positive ACT dynamics enables prognostic, spatiotemporal monitoring with unprecedented clarity and detail to facilitate comprehensive therapy evaluation with potential for clinical translation.
authors.affiliation: Molecular Imaging Innovations Institute, Department of Radiology, Weill Cornell Medicine, New York, New York, USA.|Department of Biomedical Engineering, Cornell University, Ithaca, New York, USA.
authors.forename: Yogindra
authors.initials: Y
authors.lastname: Vedvyas
authors.affiliation: Molecular Imaging Innovations Institute, Department of Radiology, Weill Cornell Medicine, New York, New York, USA.
authors.forename: Enda
authors.initials: E
authors.lastname: Shevlin
authors.affiliation: Molecular Imaging Innovations Institute, Department of Radiology, Weill Cornell Medicine, New York, New York, USA.
authors.forename: Marjan
authors.initials: M
authors.lastname: Zaman
authors.affiliation: Department of Surgery, Weill Cornell Medicine, New York, New York, USA.
authors.forename: Irene M
authors.initials: IM
authors.lastname: Min
authors.affiliation: Molecular Imaging Innovations Institute, Department of Radiology, Weill Cornell Medicine, New York, New York, USA.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Amor-Coarasa
authors.affiliation: Molecular Imaging Innovations Institute, Department of Radiology, Weill Cornell Medicine, New York, New York, USA.|Department of Biomedical Engineering, Cornell University, Ithaca, New York, USA.
authors.forename: Spencer
authors.initials: S
authors.lastname: Park
authors.affiliation: Molecular Imaging Innovations Institute, Department of Radiology, Weill Cornell Medicine, New York, New York, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Park
authors.affiliation: Molecular Imaging Innovations Institute, Department of Radiology, Weill Cornell Medicine, New York, New York, USA.
authors.forename: Keon-Woo
authors.initials: KW
authors.lastname: Kwon
authors.affiliation: Molecular Imaging Innovations Institute, Department of Radiology, Weill Cornell Medicine, New York, New York, USA.
authors.forename: Turner
authors.initials: T
authors.lastname: Smith
authors.affiliation: Molecular Imaging Innovations Institute, Department of Radiology, Weill Cornell Medicine, New York, New York, USA.
authors.forename: Yonghua
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Molecular Imaging Innovations Institute, Department of Radiology, Weill Cornell Medicine, New York, New York, USA.
authors.forename: Dohyun
authors.initials: D
authors.lastname: Kim
authors.affiliation: Molecular Imaging Innovations Institute, Department of Radiology, Weill Cornell Medicine, New York, New York, USA.|Department of Pathology, Chonnam National University Medical School, Gwangju, South Korea.
authors.forename: Young
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Molecular Imaging Innovations Institute, Department of Radiology, Weill Cornell Medicine, New York, New York, USA.
authors.forename: Benedict
authors.initials: B
authors.lastname: Law
authors.affiliation: Molecular Imaging Innovations Institute, Department of Radiology, Weill Cornell Medicine, New York, New York, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Ting
authors.affiliation: Molecular Imaging Innovations Institute, Department of Radiology, Weill Cornell Medicine, New York, New York, USA.
authors.forename: John
authors.initials: J
authors.lastname: Babich
authors.affiliation: Molecular Imaging Innovations Institute, Department of Radiology, Weill Cornell Medicine, New York, New York, USA.|Department of Biomedical Engineering, Cornell University, Ithaca, New York, USA.|Department of Surgery, Weill Cornell Medicine, New York, New York, USA.
authors.forename: Moonsoo M
authors.initials: MM
authors.lastname: Jin
mesh_terms: D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic; D017930:Genes, Reporter; D006801:Humans; D016219:Immunotherapy, Adoptive; D019169:Jurkat Cells; D051379:Mice; D009374:Neoplasms, Experimental / Q000628:therapy*; D049268:Positron-Emission Tomography; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D013601:T-Lymphocytes / Q000166:cytology*; D014161:Transduction, Genetic; D023041:Xenograft Model Antitumor Assays
chemical_list: D011948:Receptors, Antigen, T-Cell