Whole-body distribution and radiation dosimetry of [11C]telmisartan as a biomarker for hepatic organic anion transporting polypeptide (OATP) 1B3

Objectives Telmisartan, a nonpeptide angiotensin II AT1 receptor antagonist used as an antihypertensive drug, is specifically taken up by the liver through the OATP1B3. PET imaging with [11C]telmisartan is expected to provide information about the whole body pharmacokinetics of telmisartan as well as its transport property by hepatic OATP1B3. The purpose of the study was to confirm safety and to determine the biodistribution and radiation dosimetry of [11C]telmisartan in humans.

Methods Biodistribution of [11C]telmisartan was measured in three rats and six healthy male human volunteers. In the rat study, a dynamic emission scan was performed for 90 min. In the human study, dynamic whole-body PET images were acquired after intravenous injection of [11C]telmisartan. ROIs were defined for source organs on the PET images to measure time-course of [11C]telmisartan uptake as percentage injected dose and the number of disintegration for each organ. Radiation dosimetry was calculated with OLINDA/EXM.

Results In the rat study, most radioactivity was rapidly taken up by the liver and part of it was excreted into the biliary tract and intestine. Extrapolating from the rat data, the effective dose for the adult human being was estimated to be 3.72 microSv/MBq. In the human study, most of the tracer was taken up by the liver as well, although not as rapid as in the rat. The activity in the gall bladder and intestine increased gradually. Little urinary excretion was observed. The effective dose for the adult human being was 4.24 microSv/MBq based on ICRP 1990 and 4.52 microSv/MBq based on ICRP 2007 due to contribution of the gall bladder exposure.

Conclusions [11C]Telmisartan is a safe PET tracer with a dosimetry profile comparable to other common 11C PET tracers