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

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

Research output: Contribution to journalArticlepeer-review

63 Scopus citations

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.

Original languageEnglish
Pages (from-to)579-588
Number of pages10
JournalNuclear Medicine and Biology
Volume35
Issue number5
DOIs
StatePublished - Jul 2008
Externally publishedYes

Keywords

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

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