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Updated: Jun 24, 2026
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
Optical imaging of cellular immunotherapy against prostate cancer
Sidhartha Tavri1, Priyanka Jha, Reinhard Meier
1Department of Radiology, University of California-San Francisco, San Francisco, CA 941143-0628, USA.
Abstract:
The purpose of this study was to track fluorophore-labeled, tumor-targeted natural killer (NK) cells to human prostate cancer xenografts with optical imaging (OI). NK-92-scFv(MOC31)-zeta cells targeted to the epithelial cell adhesion molecule (EpCAM) antigen on prostate cancer cells and nontargeted NK-92 parental cells were labeled with the near-infrared dye DiD (1,1'-dioctadecyl-3,3,3',3'-tetramethylindodicarbocyanine). The fluorescence, viability, and cytotoxicity of the labeled cells were evaluated. Subsequently, 12 athymic rats with prostate cancer xenografts underwent OI scans before and up to 24 hours postinjection of DiD-labeled parental NK-92 cells or NK-92-scFv(MOC31)-zeta cells. The tumor fluorescence intensity was measured and compared between pre- and postinjection scans and between both groups using t-tests. OI data were confirmed with fluorescence microscopy. In vitro studies demonstrated a significant increase in the fluorescence of labeled cells compared with unlabeled controls, which persisted over a period of 24 hours without any significant change in the viability. In vivo studies demonstrated a significant increase in tumor fluorescence at 24 hours postinjection of tumor-targeted NK-92-scFv(MOC31)-zeta cells but not parental NK cells. Ex vivo OI scans and fluorescence microscopy confirmed a specific accumulation of NK-92-scFv(MOC31)-zeta cells but not parental NK cells in the tumors. Tumor-targeted NK-92-scFv(MOC31)-zeta cells could be tracked to prostate cancer xenografts with OI.
Insights
This study successfully tracked tumor-targeted natural killer (NK) cells to prostate cancer xenografts using optical imaging. Targeted NK cells showed specific accumulation in tumors, demonstrating their potential for cancer therapy monitoring.
Area of Science:
- Biomedical Imaging
- Cancer Biology
- Cell Therapy
Background:
- Natural Killer (NK) cells are crucial for immune surveillance and cancer therapy.
- Targeting NK cells to tumors can enhance their therapeutic efficacy.
- Optical imaging (OI) offers a non-invasive method for tracking cells in vivo.
Purpose of the Study:
- To evaluate the feasibility of tracking fluorophore-labeled, tumor-targeted NK cells to prostate cancer xenografts using optical imaging.
- To assess the specificity and accumulation of targeted NK cells within tumors.
- To validate the use of OI for monitoring NK cell-based cancer therapies.
Main Methods:
- NK-92 cells, engineered to target the EpCAM antigen (NK-92-scFv(MOC31)-zeta), were labeled with a near-infrared dye (DiD).
- In vitro studies assessed cell fluorescence, viability, and cytotoxicity.
- In vivo studies involved OI scans of athymic rats with prostate cancer xenografts before and after injection of labeled parental or targeted NK-92 cells.
Main Results:
- In vitro, labeled NK cells exhibited stable fluorescence for 24 hours without compromising viability.
- In vivo OI revealed significant tumor fluorescence 24 hours post-injection of targeted NK-92-scFv(MOC31)-zeta cells, but not parental NK cells.
- Ex vivo OI and fluorescence microscopy confirmed specific accumulation of targeted NK cells within tumors.
Conclusions:
- Tumor-targeted NK-92-scFv(MOC31)-zeta cells can be successfully tracked to prostate cancer xenografts using optical imaging.
- OI is a viable method for monitoring the delivery and accumulation of targeted NK cells in solid tumors.
- This approach holds promise for optimizing and evaluating NK cell-based immunotherapies for prostate cancer.
