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


CONCLUSIONS
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.
Meier
Reinhard
R
Department of Radiology, University of California-San Francisco, CA, USA. reinhardt.meier@gmail.com
Piert
Morand
M
Piontek
Guido
G
Rudelius
Martina
M
Oostendorp
Robert A
RA
Senekowitsch-Schmidtke
Reingard
R
Henning
Tobias D
TD
Wels
Winfried S
WS
Uherek
Christoph
C
Rummeny
Ernst J
EJ
Daldrup-Link
Heike E
HE
D016475:3T3 Cells; D000818:Animals; D001345:Autoradiography; D018959:CD57 Antigens / Q000378:metabolism; D045744:Cell Line, Tumor; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007150:Immunohistochemistry; D007328:Insulin / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000000981:diagnostic imaging*; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D009000:Monocytes / Q000000981:diagnostic imaging; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000000981:diagnostic imaging* / Q000235:genetics*; D015202:Protein Engineering; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*
D018959:CD57 Antigens; D019788:Fluorodeoxyglucose F18; D007004:Hypoglycemic Agents; D007328:Insulin; D019275:Radiopharmaceuticals; D018719:Erb-b2 Receptor Tyrosine Kinases; C524056:Erbb2 protein, mouse