title: Pharmacokinetic alteration of (99m)Tc-MAG3 using serum protein binding displacement method.
abstract: BACKGROUND
  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 ((99m)Tc-MAG3) using the serum protein binding displacement method.
  
  
  METHODS
  Rat and human serum protein binding rates of (99m)Tc-MAG3 were measured by ultrafiltration with or without displacers of human serum albumin (HSA) binding sites I and II (200μM and 400μM loading). Male Wistar rats were injected with (99m)Tc-MAG3 (740kBq/0.3mL saline) via the tail vein, and biodistribution was assessed at 2, 5, 10 and 15min. Dynamic whole-body images were obtained for (99m)Tc-MAG3 (11.1MBq/0.3mL saline)-injected rats, with or without HSA displacers.
  
  
  RESULTS
  (99m)Tc-MAG3 strongly bound to HSA (87.37%±2.13%). Using HSA site I displacers, the free fraction of (99m)Tc-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 240s to 110s, and from 170s to 120s.
  
  
  CONCLUSIONS
  We found that (99m)Tc-MAG3 bound to the HSA binding site I. It was confirmed that pharmacokinetic distribution of (99m)Tc-MAG3 is altered by presence of BCL, which leads to increases in the free fraction of (99m)Tc-MAG3, and BCL produced rapid blood clearance and fast peak times on rat renograms. The serum protein binding displacement method using (99m)Tc-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.
authors: School of Health Sciences, College of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Ishikawa 920-0942, Japan.
authors: Kodai
authors: K
authors: Nishi
authors: Masato
authors: M
authors: Kobayashi
authors: Ryuichi
authors: R
authors: Nishii
authors: Naoto
authors: N
authors: Shikano
authors: Norito
authors: N
authors: Takamura
authors: Noriyuki
authors: N
authors: Kuga
authors: Keishi
authors: K
authors: Yamasaki
authors: Shigeki
authors: S
authors: Nagamachi
authors: Shozo
authors: S
authors: Tamura
authors: Masaki
authors: M
authors: Otagiri
authors: Keiichi
authors: K
authors: Kawai
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D006801:Humans; D008297:Male; D011485:Protein Binding; D051381:Rats; D017208:Rats, Wistar; D012709:Serum Albumin / Q000378:metabolism*; D017263:Technetium Tc 99m Mertiatide / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics*
chemical_list: D012709:Serum Albumin; D017263:Technetium Tc 99m Mertiatide