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Impact of tamoxifen and dexamethasone on membrane fluidity and tumor targeting of lipiodol in hepatocellular carcinoma
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Edité par CCSD ; Society of Nuclear Medicine -
International audience. Objectives Lipiodol is used as a vector for chemoembolization or internal radiotherapy in unresectable hepatocellular carcinomas. 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 38 rats with hepatocellular carcinoma, which had been previously treated by dexamethasone and/or tamoxifen, after intra-arterial administration of 99mTc-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 increased tumoral uptake of lipiodol, this effect does not reach significance. On the other hand, there is a significant increase (+ 44%) in the tumoral uptake of 99mTc-SSS-lipiodol in rats pre-treated by a combination of 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<0.05).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 radiolabelled lipiodol, with a view to improving the effectiveness of hepatocellular carcinomas therapy
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