PMID- 14734684
OWN - NLM
STAT- MEDLINE
DCOM- 20040413
LR  - 20191210
IS  - 0161-5505 (Print)
IS  - 0161-5505 (Linking)
VI  - 45
IP  - 1
DP  - 2004 Jan
TI  - Augmented 18F-FDG uptake in activated monocytes occurs during the priming process 
      and involves tyrosine kinases and protein kinase C.
PG  - 124-8
AB  - Activated monocytes with a high (18)F-FDG accumulation can affect the results of 
      clinical PET studies. To better understand the mechanisms regulating monocytic 
      (18)F-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-gamma (IFN-gamma), 
      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. (18)F-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-gamma priming alone resulted in low luminescence levels (13.9% 
      +/- 4.6% of PMA-stimulated cells). In contrast, priming alone was sufficient to 
      augment monocytic (18)F-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 (18)F-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-gamma priming alone, without 
      stimulation of respiratory-burst activity, is sufficient to induce maximal 
      augmentation of (18)F-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.
FAU - Paik, Jin-Young
AU  - Paik JY
AD  - Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University 
      School of Medicine, Seoul, Korea.
FAU - Lee, Kyung-Han
AU  - Lee KH
FAU - Choe, Yearn Seong
AU  - Choe YS
FAU - Choi, Yong
AU  - Choi Y
FAU - Kim, Byung-Tae
AU  - Kim BT
LA  - eng
PT  - Comparative Study
PT  - Evaluation Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Nucl Med
JT  - Journal of nuclear medicine : official publication, Society of Nuclear Medicine
JID - 0217410
RN  - 0 (Radiopharmaceuticals)
RN  - 0Z5B2CJX4D (Fluorodeoxyglucose F18)
RN  - 56937-68-9 (phorbolol myristate acetate)
RN  - 82115-62-6 (Interferon-gamma)
RN  - EC 2.7.10.2 (src-Family Kinases)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - NI40JAQ945 (Tetradecanoylphorbol Acetate)
RN  - S88TT14065 (Oxygen)
SB  - IM
MH  - Cells, Cultured
MH  - Fluorodeoxyglucose F18/*pharmacokinetics
MH  - Humans
MH  - Interferon-gamma/*metabolism/pharmacology
MH  - Monocytes/diagnostic imaging/drug effects/metabolism
MH  - Monocytes, Activated Killer/*diagnostic imaging/drug effects/*metabolism
MH  - Oxygen/metabolism
MH  - Protein Kinase C/*metabolism
MH  - Radionuclide Imaging
MH  - Radiopharmaceuticals/pharmacokinetics
MH  - Respiratory Burst/drug effects/*physiology
MH  - Tetradecanoylphorbol Acetate/*analogs & derivatives/*pharmacology
MH  - src-Family Kinases/*metabolism
EDAT- 2004/01/22 05:00
MHDA- 2004/04/14 05:00
CRDT- 2004/01/22 05:00
PHST- 2004/01/22 05:00 [pubmed]
PHST- 2004/04/14 05:00 [medline]
PHST- 2004/01/22 05:00 [entrez]
PST - ppublish
SO  - J Nucl Med. 2004 Jan;45(1):124-8.