Evaluation Of Fluoxetine, A Potential MDR Reversal Agent In Human Lung Cancer Xenografts Using ～(99m)Tc-labeled Sestamibi

Objective: To study whether Fluoxetine can modulate tumor MDR and have an influence on someorgans in mice with human lung cancer (A549/T) xenografts by means of ^99mTc-MIBI dynamicimaging. Methods: BALB/cA-nu mice received P-gp positive cell A549/T xenografls. When thetumors' diameters were up to0.8-1.2cm, the mice were randomly divided into four groups includingcontrol group; F0.5; F1.0 and F2.0 experimental groups. A549/T -bearing mice were respectivelyinjected intraperitoneally 0.5; 1.0 and 2.0mg/kg Fluoxetine, qd×5days, in experimental groups, however, the mice were injected intraperitoneally saline in the same volume in control group. Beforeimaging studies, dynamic images were acquired every 0.5 min for the first 30 min, using a SPECTsystem. The biodistribution of MIBI was determined at the end of the imaging session.Results: A549/T xenografls could only be visualized before 8-10 min without Fluoxetine treatment butcould be detected for 30 min with Fluoxetine. A549/T xenografls with Fluoxetine treatment (F0.5; F1.0andF2.0) showed significantly lower radioactive washout than that without Fluoxetine treatment (F0).Fluoxetine increased the accumulation(%ID/g) in A549/T with increasing agent doses. Fluoxetine hasan influence on the accumulation and washout of A549/T xenograft tumor, but not influences on otherorgans, such as lung, liver, heart et al. in xenografl modes. Conclusions: Fluoxetine can increase the^99mTc-MIBI accumulation in P-gp positive tumors and the effect increased with increasing doses. AndFluoxetine does not interfere the biodistribution of MIBI in some organs.