The fact that fluorine-18 fluorodeoxyglucose ([(18)F]FDG) accumulates in inflammatory lesions as well as in tumours reduces the diagnostic specificity of positron emission tomography (PET) in oncology. The aim of this study was to characterise the uptake of [(18)F]FDG in isolated human monocyte-macrophages (HMMs) in vitro in comparison with that in human glioblastoma (GLI) and pancreatic carcinoma cells (PAN). The purity of HMM preparations was determined by immunohistochemical staining and their functional integrity was assessed by long-term incubation with iodine-131 acetylated bovine serum albumin. [(18)F]FDG uptake in HMMs was quantified as percent of whole [(18)F]FDG activity per well (% ID) or as % ID in relation to total protein mass. [(18)F]FDG uptake in HMMs significantly increased with culture duration, yielding 7.5%+/-0.9% (% ID/100 micro g) at day 14. Stimulation by lipopolysaccharide further enhanced [(18)F]FDG uptake in HMMs by a factor of 2. [(18)F]FDG uptake significantly decreased with increasing glucose concentration in the medium. Radio-thin layer chromatography of intracellular metabolites revealed that [(18)F]FDG was trapped by HMMs mainly as [(18)F]FDG-6-phosphate and [(18)F]FDG-1,6-diphosphate. [(18)F]FDG uptake was in the range of uptake values measured in GLI and PAN. By accumulating [(18)F]FDG in a manner analogous to uptake by tumour cells, activated HMMs may contribute to the [(18)F]FDG uptake values measured by PET in neoplasms.

Recent clinical evidence suggests that positron emission tomography with fluorine-18 fluorodeoxyglucose (FDG-PET) is more accurate in detecting thyroid carcinomatous tissue at high than at low TSH levels. The aim of this study was to determine the influence of TSH on FDG uptake in human thyroid cells in vitro. Monolayers of human thyroid tissue were cultured after mechanical disintegration and enzymatic digestion of samples from patients undergoing surgery for nodular goitre. The purity of thyroid cell preparations was ascertained by immunohistochemical staining for the epithelial antigen KL-1, and their viability by measuring the synthesis of thyroglobulin in vitro. The cells were incubated with 0.8-1.5 MBq FDG/ml uptake medium for 1 h. FDG uptake in thyroid cells was quantified as percent of whole FDG activity per well (% ID) or as % ID in relation to total protein mass. This experimental protocol was subsequently varied to study the effect of incubation time, glucose dependency and TSH. Furthermore, radio-thin layer chromatography was used to identify intracellular FDG metabolites. FDG accumulated in the thyroid cells linearly with time, doubling roughly every 20 min. Uptake was competitively inhibited by unlabelled glucose and decreased to approximately 70% at 100 mg/dl glucose compared to the value measured in glucose-free medium. FDG was intracellularly trapped as FDG-6 phosphate and FDG-1,6-diphosphate. TSH significantly increased FDG uptake in vitro in a time- and concentration-dependent manner: Cells cultured at a TSH concentration of 50 micro U/ ml doubled FDG uptake compared to TSH-free conditions, and uptake after 72 h of TSH pre-incubation was approximately 300% of that without TSH pre-incubation. TSH stimulates FDG uptake by benign thyroid cells in a time- and concentration-dependent manner. This supports the clinical evidence that in well-differentiated thyroid carcinomas, most of which are still TSH-sensitive, FDG-PET is more accurate at high levels of TSH.

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