Reply to the letter by Y. Ni et al. regarding ‘‘Expression of OATP1B3’’

Abstract

We thank Y. Ni and colleagues [1] for their interest and suggestions regarding our article [2]. In liver imaging, the contrast between tumorous lesions and liver parenchyma is one of the more important factors in the detection of tumorous lesions in the liver; it also plays an important role in evaluating the nature of these lesions. In clinical practice, the signal intensity (SI) of tumorous lesions is usually assessed relative the SI of the surrounding liver parenchyma, and based on this assessment, the lesion is rated as hyperintense, isointense, or hypointense. Contrast enhancement (CE) of tumorous lesions in the liver is also often assessed relative to the SI (enhancement effects) of the surrounding liver parenchyma. Our study was designed to elucidate the mechanism underlying the uptake of gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA) by hepatocellular carcinomas (HCCs). Our hypothesis was that the enhancement ratio (ER), an indicator of Gd-EOB-DTPA uptake by HCC, would provide an optimum index for assessing CE in HCCs. We therefore adopted the ER in our study. It is well known that the extent to which Gd-EOB-DTPA is taken up by the liver parenchyma cells is closely determined by the underlying hepatic function of these cells. For this reason, the observed SI in the liver parenchyma during the hepatobiliary phase is determined by the function of the liver. The value of signals such as the contrast ratio (CR) that also reflect the SI of the liver parenchyma can vary greatly depending on the extent of Gd-EOB-DTPA uptake by both the HCC and the liver parenchyma. The CE pattern also varies according to the extent of Gd-EOB-DTPA uptake by the liver parenchyma. For example, in cases of HCCs where the tumor SI changes from 300 (before infusion of the contrast agent) to 650 (after infusion of the contrast agent) (Table 1, Panel C of Ni’s article), the ER remains at 1.2 irregardless of changes in the SI (CE) of the background liver parenchyma. In CR and CE patterns, if the liver SI is \650, the CR is \1 [negative tumor contrast enhancement (TCE], but if the liver SI is [650, the CR is [1 (positive TCE). Given this background, it is evident that neither the CR or the CE pattern reflects solely the extent of Gd-EOB-DTPA uptake by HCC alone. Therefore, we believe that the ER serves as an optimum indicator of the extent of Gd-EOB-DTPA uptake by HCC. We would like to ask Y. Ni and colleagues to explain why they believe that our finding of differences in Gd-EOB-DTPA uptake being dependent on OATP1B3 expression may be insignificant. Several earlier reports have shown that the CE varies in relation to the grade of cancer differentiation. However, drugs need to pass through the cell membrane pump before they enter cells, and it is evident that drug uptake by cells varies in relation to the nature and function of the pump. Consequently, it is not 100% clear whether the degree of cancer differentiation is truly associated with drug uptake by cells. We conducted our study because we believe that a close association between the degree of cancer differentiation and drug uptake by cells cannot be accepted so long as the possible This author’s reply refers to the letter to the editor at doi: 10.1007/s00535-009-0174-z.