Radionuclide-based molecular imaging allows CAR-T cellular visualization and therapeutic monitoring

Theranostics. 2021 May 3;11(14):6800-6817. doi: 10.7150/thno.56989. eCollection 2021.

Abstract

Chimeric antigen receptor T cell (CAR-T) therapy is a new and effective form of adoptive cell therapy that is rapidly entering the mainstream for the treatment of CD19-positive hematological cancers because of its impressive effect and durable responses. Huge challenges remain in achieving similar success in patients with solid tumors. The current methods of monitoring CAR-T, including morphological imaging (CT and MRI), blood tests, and biopsy, have limitations to assess whether CAR-T cells are homing to tumor sites and infiltrating into tumor bed, or to assess the survival, proliferation, and persistence of CAR-T cells in solid tumors associated with an immunosuppressive microenvironment. Radionuclide-based molecular imaging affords improved CAR-T cellular visualization and therapeutic monitoring through either a direct cellular radiolabeling approach or a reporter gene imaging strategy, and endogenous cell imaging is beneficial to reflect functional information and immune status of T cells. Focusing on the dynamic monitoring and precise assessment of CAR-T therapy, this review summarizes the current applications of radionuclide-based noninvasive imaging in CAR-T cells visualization and monitoring and presents current challenges and strategic choices.

Keywords: chimeric antigen receptor T cell; direct labeling; endogenous cell; molecular imaging; reporter gene; side effects; therapeutic monitoring.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antigens, Neoplasm / immunology*
  • Genes, Reporter
  • Humans
  • Immunotherapy, Adoptive / methods*
  • Mice
  • Molecular Imaging / methods*
  • Neoplasms / diagnostic imaging*
  • Radioisotopes
  • Receptors, Chimeric Antigen / genetics
  • Receptors, Chimeric Antigen / immunology
  • Receptors, Chimeric Antigen / therapeutic use*
  • T-Lymphocytes / immunology*
  • Tomography, X-Ray Computed
  • Tumor Microenvironment*
  • Xenograft Model Antitumor Assays

Substances

  • Antigens, Neoplasm
  • Radioisotopes
  • Receptors, Chimeric Antigen