Longitudinal PET imaging demonstrates biphasic CAR T cell responses in survivors

JCI Insight. 2016 Nov 17;1(19):e90064. doi: 10.1172/jci.insight.90064.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cell Line, Tumor
  • Cytotoxicity, Immunologic
  • Genes, Reporter
  • Humans
  • Immunotherapy, Adoptive*
  • Jurkat Cells
  • Mice
  • Neoplasms, Experimental / therapy*
  • Positron-Emission Tomography*
  • Receptors, Antigen, T-Cell / metabolism*
  • T-Lymphocytes / cytology*
  • Transduction, Genetic
  • Xenograft Model Antitumor Assays


  • Receptors, Antigen, T-Cell