RT Journal Article
SR Electronic
T1 In Vitro Studies on the Signal Transduction of Thyroidal Uptake of <sup>18</sup>F-FDG and <sup>131</sup>I-Iodide
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1382
OP 1388
VO 47
IS 8
A1 Bläser, Daniel
A1 Maschauer, Simone
A1 Kuwert, Torsten
A1 Prante, Olaf
YR 2006
UL http://jnm.snmjournals.org/content/47/8/1382.abstract
AB Glucose metabolism in radioiodine-negative metastases of differentiated thyroid carcinomas (DTC) may still be increased by thyroid-stimulating hormone (TSH) as demonstrated by PET with 18F-FDG. The mechanisms of signal transduction involved in that process are as yet not completely understood. Therefore, the aim of this study was to investigate the effects of TSH, of an analog of cyclic adenosine monophosphate (dibutyryl cyclic AMP (Bu)2cAMP), and of inhibitors of the phosphatidylinositol 3-kinase (PI3-kinase) and of the protein kinase A (PKA) on 18F-FDG and radioiodide uptake in the thyroid cell line FRTL-5. Methods: FRTL-5 cells were cultured in the presence of hormones with or without 1 mU/ mL TSH. Glucose carrier (GLUT-1) was determined by Western blot analysis. Cells were incubated with 0.5–1.0 MBq/mL 18F-FDG for 1 h or 18–37 kBq/mL 131I for 45 min, respectively, and tracer uptake was related to protein concentration. (Bu)2cAMP (1 mmol/L) was used as cAMP enhancer, H89 (0.25–25 μmol/L) as selective PKA inhibitor, and wortmannin (1 μmol/L) as inhibitor of PI3-kinase. Results: TSH induced a 2.6-fold ± 0.5 increase of radioiodide uptake in FRTL-5 cells (P &lt; 0.001, n = 8). The use of wortmannin inhibited TSH-induced uptake of 131I only moderately by 21.1% ± 3.5% (P &lt; 0.05, n = 8), whereas H89 markedly blocked the effect of TSH by 53.8% ± 16.7% (P &lt; 0.001, n = 8). TSH enhanced GLUT-1 concentration of FRTL-5 cell membrane preparations by a factor of 1.6 (n = 3). TSH-treated cells showed a 2.6-fold increased uptake of 18F-FDG (P &lt; 0.001, n = 20). Stimulation by (Bu)2cAMP analogously increased 18F-FDG uptake (P &lt; 0.001, n = 20). Wortmannin, but not H89, significantly inhibited TSH- and (Bu)2cAMP-stimulation of 18F-FDG uptake by 42% ± 25% (P &lt; 0.001, n = 20) and 42% ± 31% (P &lt; 0.001, n = 20), respectively. Conclusion: The effect of TSH and cAMP on 18F-FDG uptake by FRTL-5 cells is mediated by PI3-kinase and not by PKA, thus differing from the mechanism of radioiodide accumulation of this cell line. This observation is one possible explanation for the persistence of TSH-dependent 18F-FDG uptake in radioiodine-negative metastases of DTC.