gms | German Medical Science

To evaluate the clinical meaning of multidrug transporter proteins in disposition, efficacy and safety of many drugs, pharmacogenomic and drug interaction studies using suitable probe drugs have been applied so far. A more recent approach to quantify multidrug transporter functions (e.g. P-glycoprotein, MRP2) is visualization of the transport with imaging tools as positron emission tomography using [11C]-verapamil or gamma scintigraphy using 99mTc-sestamibi and 99mTc-mebrofenin as probe drugs.

Another powerful method is contrast enhancing magnetic resonance (MR) imaging using the contrast agent gadotrexate (Primovist®) that is selectively extracted after intravenous bolus injection into the liver. By gadotrexate enhancing, the detection rate of focal liver lesions can be improved.

Gadotrexate is a substrate for human MRP2, MRP3, OATP1A2, 1B1 and 1B3 but not for OATP2B1, OCT3 and ASBT as shown by in-vitro experiments using transporter-overexpressing cell models (MDCK2, HEK293) and by MR-imaging in Mrp2-deficient rats. Hepatic enhancement can be influenced by OATP-inhibitors and genetic loss-of-function polymorphisms of OATP1B1 and 1B3. There is evidence that the regional hepatic uptake in focal liver lesion is correlated to the regional expression of hepatic uptake transporter. The agent is not suitable for imaging of gall ways as its hepatic secretion is altered in patients with chronic obstructive biliary diseases. Whether gadotrexate is suitable to visualize OATP-expression in cancer tissue (e.g. prostate, breast) needs further evaluation.

In summary, uptake function of specific hepatic OATPs can be indirectly evaluated using gadotrexate contrast enhancing MR imaging.