Nuclear Imaging of CAR T Immunotherapy to Solid Tumors: In Terms of Biodistribution, Viability, and Cytotoxic Effect.

Abstract

Immunotherapy has become a mainstay of cancer therapy. Since chimeric antigen receptor (CAR) T immunotherapy achieves unprecedented success in curing hematological malignancies, the possibility of it revolutionizing the paradigm of solid tumors has aroused increasing attention. However, the restricted accessibility to tumor parenchyma, the immunosuppressive tumor microenvironment, and antigen heterogeneity of solid tumors make it difficult to replicate its success. Therefore, dynamic evaluation of CAR T cells' tumor accessibility, intratumoral viability, and anti-tumor cytotoxicity is necessary to facilitate its translation to solid tumors. Besides, real-timely imaging above events in vivo can help evaluate therapeutic responses and optimize CAR T immunotherapy for solid tumors. Nuclear imaging, including positron emission tomography (PET) and single-photon emission computed tomography (SPECT) imaging, is frequently applied for evaluating adoptive cell therapies owing to its excellent sensitivity, high tissue penetration, and great translation potential. In addition, quantitative analysis can be performed in dynamic and noninvasive patterns. This review focuses on recent advances in PET/SPECT technologies and imaging probes in monitoring CAR T cells' migration, viability, and cytotoxicity to solid tumors post-administration. Prospects of what should be done in the next stage to promote CAR T therapy's application in solid tumors are also discussed.