Spatiotemporal PET Imaging Reveals Differences in CAR-T Tumor Retention in Triple-Negative Breast Cancer Models

Mol Ther. 2020 Oct 7;28(10):2271-2285. doi: 10.1016/j.ymthe.2020.06.028. Epub 2020 Jun 27.


Chimeric antigen receptor T cell therapy (CAR-T) has been rolled out as a new treatment for hematological malignancies. For solid tumor treatment, CAR-T has been disappointing so far. Challenges include the quantification of CAR-T trafficking, expansion and retention in tumors, activity at target sites, toxicities, and long-term CAR-T survival. Non-invasive serial in vivo imaging of CAR-T using reporter genes can address several of these challenges. For clinical use, a non-immunogenic reporter that is detectable with exquisite sensitivity by positron emission tomography (PET) using a clinically available non-toxic radiotracer would be beneficial. Here, we employed the human sodium iodide symporter to non-invasively quantify tumor retention of pan-ErbB family targeted CAR-T by PET. We generated and characterized traceable CAR T cells and examined potential negative effects of radionuclide reporter use. We applied our platform to two different triple-negative breast cancer (TNBC) models and unexpectedly observed pronounced differences in CAR-T tumor retention by PET/CT (computed tomography) and confirmed data ex vivo. CAR-T tumor retention inversely correlated with immune checkpoint expression in the TNBC models. Our platform enables highly sensitive non-invasive PET tracking of CAR-T thereby addressing a fundamental unmet need in CAR-T development and offering to provide missing information needed for future clinical CAR-T imaging.

Keywords: CAR; PET imaging; cell tracking; chimeric antigen receptor; immune checkpoint; immunotherapy; reporter gene; triple-negative breast cancer; tumour retention.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Combined Modality Therapy
  • Disease Models, Animal
  • Female
  • Humans
  • Immune Checkpoint Inhibitors / pharmacology
  • Immunotherapy, Adoptive*
  • Molecular Imaging
  • Positron Emission Tomography Computed Tomography / methods
  • Positron-Emission Tomography*
  • Receptors, Antigen, T-Cell / immunology*
  • Receptors, Chimeric Antigen / immunology*
  • Treatment Outcome
  • Triple Negative Breast Neoplasms / diagnosis*
  • Triple Negative Breast Neoplasms / therapy*
  • Xenograft Model Antitumor Assays


  • Immune Checkpoint Inhibitors
  • Receptors, Antigen, T-Cell
  • Receptors, Chimeric Antigen