Tracking of [18F]FDG-labeled natural killer cells to HER2/neu-positive tumors

Meier, Reinhard; Piert, Morand; Piontek, Guido; Rudelius, Martina; Oostendorp, Robert A.; Senekowitsch-Schmidtke, Reingard; Henning, Tobias D.; Wels, Winfried S.; Uherek, Christoph; Rummeny, Ernst J.; Daldrup-Link, Heike E.

doi:10.1016/j.nucmedbio.2008.02.006

« Previous Next »Nuclear Medicine and Biology
Volume 35, Issue 5 , Pages 579-588, July 2008

Tracking of [¹⁸F]FDG-labeled natural killer cells to HER2/neu-positive tumors

Reinhard Meier
- Department of Radiology, University of California San Francisco, USA
- Corresponding author. Tel.: +49 178 7879781.
Morand Piert
- Department of Radiology, Division of Nuclear Medicine, University of Michigan, USA
Guido Piontek
- Institute of Pathology, Klinikum rechts der Isar, Technische Universität München, Germany
Martina Rudelius
- Institute of Pathology, Klinikum rechts der Isar, Technische Universität München, Germany
Robert A. Oostendorp
- 3rd Department of Internal Medicine, Klinikum rechts der Isar, Technische Universität München, Germany
Reingard Senekowitsch-Schmidtke
- Department of Nuclear Medicine, Klinikum rechts der Isar, Technische Universität München, Germany
Tobias D. Henning
- Department of Radiology, University of California San Francisco, USA
Winfried S. Wels
- Chemotherapeutisches Forschungsinstitut, Georg-Speyer-Haus, Frankfurt am Main, Germany
Christoph Uherek
- Chemotherapeutisches Forschungsinstitut, Georg-Speyer-Haus, Frankfurt am Main, Germany
Ernst J. Rummeny
- Department of Radiology, Klinikum rechts der Isar, Technische Universität München, Germany
Heike E. Daldrup-Link
- Department of Radiology, University of California San Francisco, USA

Received 6 October 2007; received in revised form 8 February 2008; accepted 28 February 2008. published online 06 May 2008.

Abstract

Introduction

The objective of this study was to label the human natural killer (NK) cell line NK-92 with [¹⁸F]fluoro-deoxy-glucose (FDG) for subsequent in vivo tracking to HER2/neu-positive tumors.

Methods

NK-92 cells were genetically modified to NK-92-scFv(FRP5)-zeta cells, which express a chimeric antigen receptor that is specific to the tumor-associated ErbB2 (HER2/neu) antigen. NK-92 and NK-92-scFv(FRP5)-zeta cells were labeled with [¹⁸F]FDG by simple incubation at different settings. Labeling efficiency was evaluated by a gamma counter. Subsequently, [¹⁸F]FDG-labeled parental NK-92 or NK-92-scFv(FRP5)-zeta cells were intravenously injected into mice with implanted HER2/neu-positive NIH/3T3 tumors. Radioactivity in tumors was quantified by digital autoradiography and correlated with histopathology.

Results

The NK-92 and NK-92-scFv(FRP5)-zeta cells could be efficiently labeled with [¹⁸F]FDG by simple incubation. Optimal labeling efficiencies (80%) were achieved using an incubation period of 60 min and additional insulin (10 IU/ml). After injection of 5×10⁶ [¹⁸F]FDG-labeled NK-92-scFv(FRP5)-zeta cells into tumor-bearing mice, digital autoradiography showed an increased uptake of radioactivity in HER2/neu-positive tumors at 60 min postinjection. Conversely, injection of 5×10⁶ NK-92 cells not directed against HER2/neu receptors did not result in increased uptake of radioactivity in the tumors. Histopathology confirmed an accumulation of the NK-92-scFv(FRP5)-zeta cells, but not the parental NK cells, in tumor tissues.

Conclusion

The human NK cell line NK-92 can be directed against HER2/neu antigens by genetic modification. The genetically modified NK cells can be efficiently labeled with [¹⁸F]FDG, and the accumulation of these labeled NK cells in HER2/neu-positive tumors can be monitored with autoradiography.

Keywords: 18F-2-fluoro-2-deoxyl-D-glucose, Autoradiography, Biodistribution, Molecular imaging, Cell targeting, NK cells