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

Nucl Med Biol. 2008 Jul;35(5):579-88. doi: 10.1016/j.nucmedbio.2008.02.006. Epub 2008 May 2.


Introduction: The objective of this study was to label the human natural killer (NK) cell line NK-92 with [(18)F]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 [(18)F]FDG by simple incubation at different settings. Labeling efficiency was evaluated by a gamma counter. Subsequently, [(18)F]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 [(18)F]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 5x10(6) [(18)F]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 5x10(6) 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 [(18)F]FDG, and the accumulation of these labeled NK cells in HER2/neu-positive tumors can be monitored with autoradiography.

MeSH terms

  • 3T3 Cells
  • Animals
  • Autoradiography
  • CD57 Antigens / metabolism
  • Cell Line, Tumor
  • Female
  • Fluorodeoxyglucose F18*
  • Humans
  • Hypoglycemic Agents / pharmacology
  • Immunohistochemistry
  • Insulin / pharmacology
  • Killer Cells, Natural / diagnostic imaging*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Nude
  • Monocytes / diagnostic imaging
  • Neoplasm Transplantation
  • Neoplasms, Experimental / diagnostic imaging*
  • Neoplasms, Experimental / genetics*
  • Protein Engineering
  • Radionuclide Imaging
  • Radiopharmaceuticals*
  • Receptor, ErbB-2 / genetics*


  • CD57 Antigens
  • Hypoglycemic Agents
  • Insulin
  • Radiopharmaceuticals
  • Fluorodeoxyglucose F18
  • Erbb2 protein, mouse
  • Receptor, ErbB-2