AUTHOR=Mulgaonkar Aditi , Udayakumar Durga , Yang Yaxing , Harris Shelby , Öz Orhan K. , Ramakrishnan Geethakumari Praveen , Sun Xiankai 

TITLE=Current and potential roles of immuno-PET/-SPECT in CAR T-cell therapy

JOURNAL=Frontiers in Medicine

VOLUME=Volume 10 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2023.1199146

DOI=10.3389/fmed.2023.1199146

ISSN=2296-858X

ABSTRACT=Chimeric antigen receptor (CAR) T-cell therapies have evolved as breakthrough treatment options for management of hematological malignancies and are also being developed as therapeutics for solid tumors. However, despite impressive patient responses seen with CD19 directed CAR T-cell therapeutics, approximately 40 - 60% of these patients’ cancers eventually relapse with variable prognosis. Such relapses may occur due to a combination of molecular resistance mechanisms including antigen loss or mutations, T-cell exhaustion, and progression of the immunosuppressive tumor microenvironment. This class of therapeutics is also associated with some unique toxicities such as cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, and other “on-target, off-tumor” toxicities, and anaphylaxis effects. Furthermore, manufacturing limitations and challenges associated with solid tumor infiltration have delayed extensive applications. Immunological positron emission tomography or single-photon emission computed tomography (Immuno-PET/-SPECT) molecular imaging modalities offer a target-specific and highly sensitive quantitative noninvasive platform for longitudinal detection of dynamic variations in target antigen expression in the body. Leveraging these imaging strategies as guidance tools with CAR T-cell therapeutics may enable timely identification of resistance mechanisms and/or toxic events when they occur, permitting rationalized application of effective therapeutic interventions. In addition, utilizing these approaches for tracking the CAR T-cell pharmacokinetics, during product development optimization, may help to assess their efficacy and accordingly predict treatment outcomes. In this review, we focused on the current challenges and potential opportunities for application of immuno-PET/-SPECT imaging strategies to address the challenges encountered with the CAR T-cell therapies.