Introduction: When-a radiopharmaceutical is simultaneously administered with a medicine that has high affinity for the same plasma protein, the radiopharmaceutical is released at higher concentrations in blood, leading to enhanced transfer into target tissues. This is known as the serum protein binding displacement method. In this study, we investigated the pharmacokinetic alteration of technetium-99m-labeled mercaptoacetylglycylglycylglycine (Tc-99m-MAG3) using the serum protein binding displacement method.
Methods: Rat and human serum protein binding rates of Tc-99m-MAG3 were measured by ultrafiltration with or without displacers of human serum albumin (HSA) binding sites land II (200 mu M and 400 mu M loading). Male Wistar rats were injected with Tc-99m-MAG3 (740 kBq/0.3 mL saline) via the tail vein, and biodistribution was assessed at 2, 5, 10 and 15 min. Dynamic whole-body images were obtained for Tc-99m-MAG3 (11.1 MBq/0.3 mL saline)-injected rats, with or without HSA displacers.
Results: Tc-99m-MAG3 strongly bound to HSA (87.37%+/- 2.13%). Using HSA site I displacers, the free fraction of Tc-99m-MAG3 increased significantly (1.20 to 1.47 times) when compared with controls. For biodistribution and imaging, rapid blood clearance was observed with bucolome (BCL) loading, which is an HSA site I displacer. With BCL loading, peak times for rat renograms were respectively shifted from 240 s to 110 s, and from 170 s to 120 s.
Conclusions: We found that Tc-99m-MAG3 bound to the HSA binding site I. It was confirmed that pharmacokinetic distribution of Tc-99m-MAG3 is altered by presence of BCL, which leads to increases in the free fraction of Tc-99m-MAG3, and BCL produced rapid blood clearance and fast peak times on rat renograms. The serum protein binding displacement method using Tc-99m-MAG3 and BCL, a safe displacer for humans, may be applicable to clinical study and lead to better diagnostic images with shorter waiting times and lower radiation doses for patients. (C) 2013 Elsevier Inc. All rights reserved.