The interaction of imatinib mesilate with P-glycoprotein (P-gp) was examined using pig kidney epithelial LLC-PK1 cells versus L-MDR1 cells, which overexpress human P-gp on the apical membrane. The basal-to-apical transport of imatinib mesilate in L-MDR1 cells significantly exceeded that in the parental LLC-PK1 cells. The intracellular accumulation of imatinib mesilate after its basal application to LLC-PK1 and L-MDR1 cells was 35% and 15%, respectively. A P-gp modulator, cyclosporin A, inhibited the basal-to-apical transport in L-MDR1 cells. The intracellular accumulation of imatinib mesilate in L-MDR1 cells was also increased by cyclosporin A. The rhodamine 123 efflux assay showed that the efflux of rhodamine 123 in K562/DXR cells, which overexpress human P-gp, could be blocked markedly by imatinib mesilate in a dose-dependent fashion. The K i values for the inhibition of P-gp function by cyclosporin A and imatinib mesilate were estimated to be 6.1 and 18.3 M, respectively, using a calcein-AM efflux assay. These observations demonstrate that imatinib mesilate is a substrate as well as a modulator of human P-gp, suggesting that imatinib mesilate drug interactions may occur via P-gp. It is necessary to consider the pharmacokinetic and pharmacodynamic interactions of imatinib mesilate with other drugs via P-gp.

We evaluated the degree of inhomogeneities of fat suppression by using the fully automated three-dimensional breast shimming technique (Image Based-Smart: IB-Smart) and manual setting of a rectangular parallelepiped shim (volume shimming) in MR mammography. Information on breast shape was collected from 9 patients whose images were insufficiently fat-suppressed. A breast phantom made of a

SummaryWhile radiography provides us clinically valuable information, it increases the risk of radiation exposure. Previous studies have reported great variations in radiation doses among institutions. It is concerning that radiation doses will increase and vary greatly from institution to institution when digital radiographic modalities become more common. In the present study, we measured chest and abdominal radiation doses at 10 institutions that had X-ray digital imaging systems. Differences in radiation doses among the institutions were evaluated and compared with the previous reports. The image quality at the measured radiation doses were also evaluated. The doses were measured by the same dosimeter, and the image quality at a specific dose was evaluated using the standard deviation of the digital values and Wiener spectrum. Our results indicate that the difference in radiation among institutions was approximately five-fold at a maximum and smaller than the previous reports had indicated. The image quality was improved as the dose was increased. We considered the five-fold difference to be the result of variations in optimum image quality and associated radiation doses among institutions. In summary, evaluating the radiation dose along with the image quality is important to optimize the doses.