Abstract
Activated monocytes with a high 18F-FDG accumulation can affect the results of clinical PET studies. To better understand the mechanisms regulating monocytic 18F-FDG uptake, we investigated the effect of priming and respiratory-burst generation and further evaluated the role of potential protein kinase pathways. Methods: Purified human monocytes were primed with interferon-γ (IFN-γ), and respiratory burst was generated by stimulation of primed cells with phorbol-12-myristate-13-acetate (PMA). Oxygen-intermediate generation was assessed by luminescence measurements after the addition of lucigenin. 18F-FDG uptake after 30 min of incubation was measured for unprimed control cells, primed cells, and PMA-stimulated cells. The role of protein kinases was investigated using respective inhibitors. Results: PMA stimulation of primed monocytes dramatically increased oxygen-intermediate generation, leading to a 42.2 ± 1.1 fold higher level of cumulative luminescence compared with unprimed control cells, whereas IFN-γ priming alone resulted in low luminescence levels (13.9% ± 4.6% of PMA-stimulated cells). In contrast, priming alone was sufficient to augment monocytic 18F-FDG uptake to 273.3% ± 16.7% of control levels (P < 0.001), and it was not further increased by PMA stimulation. The tyrosine kinase inhibitor, genistein, and the specific protein kinase C inhibitor, staurosporine, completely abolished the priming-induced enhancement of 18F-FDG uptake and lowered uptake to control levels. Under the same conditions, wortmannin, a phosphatidylinositol 3 kinase (PI3 kinase)-specific inhibitor, and cycloheximide, a protein synthesis inhibitor, were associated with only minor reductions in the enhanced-uptake effect of priming. Conclusion: IFN-γ priming alone, without stimulation of respiratory-burst activity, is sufficient to induce maximal augmentation of 18F-FDG uptake in monocytes. Furthermore, this metabolic effect appears to involve tyrosine kinases and the protein kinase C pathway but is independent of the PI3 kinase pathway.
Footnotes
Received May 19, 2003; revision accepted Sep. 25, 2003.
For correspondence or reprints contact: Kyung-Han Lee, MD, Department of Nuclear Medicine, Samsung Medical Center, 50 Ilwondong, Kangnamgu, Seoul, Korea.
E-mail: khleenm{at}samsung.co.kr