Noninvasive Imaging of Tumor-Infiltrating Lymphocytes

The rapidly advancing field of cancer immunotherapy is currently limited by the scarcity of noninvasive and quantitative technologies capable of monitoring the presence and abundance of CD8+ T cells and other immune cell subsets. In this study, we describe the generation of 89Zr-desferrioxamine–labeled anti-CD8 cys-diabody (89Zr-malDFO-169 cDb) for noninvasive immuno-PET tracking of endogenous CD8+ T cells. We demonstrate that anti-CD8 immuno-PET is a sensitive tool for detecting changes in systemic and tumor-infiltrating CD8 expression in preclinical syngeneic tumor immunotherapy models including antigen-specific adoptive T-cell transfer, agonistic antibody therapy (anti-CD137/4-1BB), and checkpoint blockade antibody therapy (anti–PD-L1). The ability of anti-CD8 immuno-PET to provide whole body information regarding therapy-induced alterations of this dynamic T-cell population provides new opportunities to evaluate antitumor immune responses of immunotherapies currently being evaluated in the clinic. Cancer Res; 76(1); 73–82. ©2015 AACR.

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