Increased Lipiodol uptake in hepatocellular carcinoma possibly due to increased membrane fluidity by dexamethasone and tamoxifen.
BACKGROUND
Lipiodol is used as a vector for chemoembolization or internal radiotherapy in unresectable hepatocellular carcinomas (HCCs). The aim of this study is to improve the tumoral uptake of Lipiodol by modulating membrane fluidizing agents to optimize the effectiveness of Lipiodol vectorized therapy.


METHODS
The effect of dexamethasone and tamoxifen on membrane fluidity was studied in vitro by electron paramagnetic resonance applied to rat hepatocarcinoma cell line N1S1. The tumoral uptake of Lipiodol was studied in vivo on rats with HCC, which had been previously treated by dexamethasone and/or tamoxifen, after intra-arterial administration of (99m)Tc-SSS-Lipiodol.


RESULTS
The two molecules studied here exhibit a fluidizing effect in vitro which appears dependent on time and dose, with a maximum fluidity obtained after 1 hr at concentrations of 20 μM for dexamethasone and 200 nM for tamoxifen. In vivo, while the use of dexamethasone or tamoxifen alone tends to lead to increased tumoral uptake of Lipiodol, this effect does not reach levels of significance. On the other hand, there is a significant increase in the tumoral uptake of (99m)Tc-SSS-Lipiodol in rats pretreated by both dexamethasone and tamoxifen, with a tumoral uptake (expressed in % of injected activity per g of tumor) of 13.57 ± 3.65% after treatment, as against 9.45 ± 4.44% without treatment (P<.05).


CONCLUSIONS
Dexamethasone and tamoxifen fluidify the N1S1 cells membrane, leading to an increase in the tumoral uptake of Lipiodol. These drugs could be combined with chemo-Lipiodol-embolization or radiolabeled Lipiodol, with a view to improving the effectiveness of HCCs therapy.
Becker
Stéphanie
S
Department of Nuclear Medicine, Centre E. Marquis, F-35042 Rennes, France. stephanie.becker@rouen.fnclcc.fr
Ardisson
Valérie
V
Lepareur
Nicolas
N
Sergent
Odile
O
Bayat
Sahar
S
Noiret
Nicolas
N
Gaboriau
François
F
Clément
Bruno
B
Boucher
Evelyne
E
Raoul
Jean-Luc
JL
Garin
Etienne
E
D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology*; D004578:Electron Spin Resonance Spectroscopy; D004998:Ethiodized Oil / Q000493:pharmacokinetics*; D007269:Injections, Intra-Arterial; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D008560:Membrane Fluidity / Q000187:drug effects*; D051381:Rats; D013629:Tamoxifen / Q000494:pharmacology*; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D013629:Tamoxifen; D003907:Dexamethasone; D004998:Ethiodized Oil