Pharmacokinetics of the phosphatidylserine tracers

Background: Phosphatidylserine (PS) is a phospholipid normally located in the inner leaflet of the cell membrane. PS is translocated from the inner to the outer leaflet of the plasma membrane during the early stages of apoptosis and in necrosis. In cell and animal studies, reversible PS externalisation to the outer membrane leaflet has been observed in viable cells. Hence, PS markers have been proposed as markers of both reversibly and irreversibly damaged cells. The purpose of this experimental study in pigs was to investigate the kinetics of the newly introduced PS marker technetium-99m-labelled lactadherin (Tc-lactadherin) in comparison with the well-known PS tracer Tc-annexin V with special reference to the renal handling of the tracers. The effective dose for humans was estimated from the biodistribution in 24 mice. Methods: Nine anaesthetised pigs randomly allocated into two treatment groups were administered a single injection of either Tc-lactadherin or Tc-annexin V. Renal perfusion was assessed by simultaneous injection of Cr-EDTA. Throughout the examinations, planar, dynamic scintigraphy of the trunk was performed, urine was collected and arterial and renal vein blood was sampled. The effective dose was estimated using the adult male phantom from the RADAR website. Results: Tc-lactadherin was cleared four times faster from plasma than Tc-annexin V, 57 ± 13 ml/min (mean ± SD) versus 14 ± 2 ml/min. Tc-lactadherin had a predominant uptake in the liver, whereas Tc-annexin V was primarily taken up by the kidneys. The estimated effective human dose after single injection of Tc-lactadherin and Tc-annexin V was 5.8 and 11 μSv/MBq, respectively. Conclusions: The high hepatic uptake of Tc-lactadherin compromises the use of Tc-lactadherin for imaging PS externalisation in the liver. Due to scatter from the liver, the use of in vivo visualisation of PS externalisation in the lower thorax and upper abdomen by Tc-lactadherin is challenged, but not precluded. In contrast to Tc-annexin, Tc-lactadherin has a low renal uptake and may be the preferred tracer for imaging PS externalisation in the kidneys. The effective dose after injection of Tc-lactadherin and Tc-annexin was low. Recommendations regarding the clinical use of Tc-lactadherin must await tracer kinetic studies in patients.