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

• Published in: Nuclear medicine and biology 2008-07, Vol.35 (5), p.579-588
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: 18F-2-fluoro-2-deoxyl-D-glucose; 3T3 Cells; Animals; Autoradiography; Biodistribution; CD57 Antigens - metabolism; Cell Line, Tumor; Cell targeting; Female; Fluorodeoxyglucose F18; Humans; Hypoglycemic Agents - pharmacology; Immunohistochemistry; Insulin - pharmacology; Killer Cells, Natural - diagnostic imaging; Mice; Mice, Inbred C57BL; Mice, Nude; Molecular imaging; Monocytes - diagnostic imaging; Neoplasm Transplantation; Neoplasms, Experimental - diagnostic imaging; Neoplasms, Experimental - genetics; NK cells; Protein Engineering; Radiology; Radionuclide Imaging; Radiopharmaceuticals; Receptor, ErbB-2 - genetics
• ISSN: 0969-8051; 1872-9614
• DOI: 10.1016/j.nucmedbio.2008.02.006

Abstract 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 5×106 [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 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 [18 F]FDG, and the accumulation of these labeled NK cells in HER2/neu-positive tumors can be monitored with autoradiography.