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
Department of Radiology, University of California-San Francisco, CA, USA.
Nucl Med Biol. 2008 Jul;35(5):579-88. doi: 10.1016/j.nucmedbio.2008.02.006. Epub 2008 May 2.
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.
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.
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.
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.
本研究的目的是用[¹⁸F]氟脱氧葡萄糖（FDG）标记人自然杀伤（NK）细胞系NK - 92，以便随后在体内追踪至HER2/neu阳性肿瘤。
将NK - 92细胞基因改造为NK - 92 - scFv(FRP5)-ζ细胞，该细胞表达一种对肿瘤相关的ErbB2（HER2/neu）抗原具有特异性的嵌合抗原受体。通过在不同条件下简单孵育，用[¹⁸F]FDG标记NK - 92和NK - 92 - scFv(FRP5)-ζ细胞。用γ计数器评估标记效率。随后，将[¹⁸F]FDG标记的亲本NK - 92或NK - 92 - scFv(FRP5)-ζ细胞静脉注射到植入了HER2/neu阳性NIH/3T3肿瘤的小鼠体内。通过数字放射自显影对肿瘤中的放射性进行定量，并与组织病理学相关联。
通过简单孵育，NK - 92和NK - 92 - scFv(FRP5)-ζ细胞能够被[¹⁸F]FDG有效标记。孵育60分钟并添加额外胰岛素（10 IU/ml）可实现最佳标记效率（80%）。将5×10⁶个[¹⁸F]FDG标记的NK - 92 - scFv(FRP5)-ζ细胞注射到荷瘤小鼠体内后，数字放射自显影显示注射后60分钟HER2/neu阳性肿瘤中放射性摄取增加。相反，注射5×10⁶个不针对HER2/neu受体的NK - 92细胞并未导致肿瘤中放射性摄取增加。组织病理学证实NK - 92 - scFv(FRP5)-ζ细胞而非亲本NK细胞在肿瘤组织中积聚。
人NK细胞系NK - 92可通过基因改造靶向HER2/neu抗原。基因改造后的NK细胞可用[¹⁸F]FDG有效标记，并且这些标记的NK细胞在HER2/neu阳性肿瘤中的积聚可通过放射自显影进行监测。
