Depicting adoptive immunotherapy for prostate cancer in an animal model with magnetic resonance imaging

Genetically modified natural killer (NK) cells that recognize tumor‐associated surface antigens have recently shown promise as a novel approach for cancer immunotherapy. To determine NK cell therapy response early, a real‐time, noninvasive method to quantify NK cell homing to the tumor is desirable. The purpose of this study was to evaluate if MR imaging could provide a noninvasive, in vivo diagnosis of NK cell accumulation in epithelial cell adhesion molecule (EpCAM)‐positive prostate cancers in a rat xenograft model. Genetically engineered NK‐92‐scFv(MOC31)‐ζ cells, which express a chimeric antigen receptor specific to the tumor‐associated EpCAM antigen, and nontargeted NK‐92 cells were labeled with superparamagnetic particles of iron‐oxides (SPIO) ferumoxides. Twelve athymic rats with implanted EpCAM positive DU145 prostate cancers received intravenous injections of 1.5 × 10⁷ SPIO labeled NK‐92 and NK‐92‐scFv(MOC31)‐ζ cells. EpCAM‐positive prostate cancers demonstrated a progressive and a significant decline in contrast‐to‐noise‐ratio data at 1 and 24 h after injection of SPIO‐labeled NK‐92‐scFv(MOC31)‐ζ cells. Conversely, tumor contrast‐to‐noise‐ratio data did not change significantly after injection of SPIO‐labeled parental NK‐92 cells. Histopathology confirmed an accumulation of the genetically engineered NK‐92‐scFv(MOC31)‐ζ cells in prostate cancers. Thus, the presence or absence of a tumor accumulation of therapeutic NK cells can be monitored with cellular MR imaging. EpCAM‐directed, SPIO labeled NK‐92‐scFv(MOC31)‐ζ cells accumulate in EpCAM‐positive prostate cancers. Magn Reson Med, 2011. © 2010 Wiley‐Liss, Inc.