title: Evaluation of Tc-99m (V) DMSA binding to human plasma proteins.
abstract: As a critical step toward elucidating the mechanism of localization of Tc-99m (V) dimercaptosuccinic acid (DMSA), we investigated its binding and transport in blood in comparison with Ga-67 citrate. The studies were performed in vitro by incubating Tc-99m (V) DMSA with blood (one sample at 4 degrees Celcius and another at 37 degrees Celcius) to assess its binding to plasma proteins using ultrafiltration, dialysis, electrophoresis, gel filtration chromatography and affinity chromatography. A parallel experiment for determining the blood binding of Ga-67 citrate was performed using the same procedures. Using ultrafiltration, dialysis, electrophoresis and gel filtration chromatography, labeled plasma samples showed that protein binding for Tc-99m (V) DMSA was 45-54% at 37 degrees Celcius and 73-80% at 4 degrees Celcius. The figures for Ga-67 citrate were 43-53% at 37 degrees Celcius and 75-81% at 4 degrees Celcius. Electrophoresis showed that Tc-99m (V) DMSA was mostly bound to plasma albumin (36.05 +/- 2.48% at 37 degrees Celcius and 60.04 +/- 1.87% at 4 degrees Celcius), and that the proportion of Ga-67 radioactivity associated with beta-globulin was 34.23 +/- 1.37% at 37 degrees Celcius and 55.71 +/- 3.69% at 4 degrees Celcius. In affinity chromatography experiments, Tc-99m (V) DMSA did not bind to transferrin, unlike Ga-67 citrate. This study demonstrates that, at the radiopharmaceutical tracer level, most Tc-99m (V) DMSA in blood is protein-bound, primarily to albumin, but not to transferrin. In contrast, Ga-67 citrate was bound primarily to transferrin. The knowledge that albumin is the main transport protein of Tc-99m (V) DMSA may contribute to a better understanding of its biodistribution and pharmacokinetics.
authors.affiliation: Department of Nuclear Medicine, National Cheng Kung University Hospital, Tainan, Taiwan. bflee@mail.ncku.edu.tw
authors.forename: Bi-Fang
authors.initials: BF
authors.lastname: Lee
authors.forename: Jwu-Lai
authors.initials: JL
authors.lastname: Yeh
authors.forename: Nan-Tsing
authors.initials: NT
authors.lastname: Chiu
authors.forename: Gin-Chung
authors.initials: GC
authors.lastname: Liu
authors.forename: Hsin-Su
authors.initials: HS
authors.lastname: Yu
authors.forename: Mei-Hui
authors.initials: MH
authors.lastname: Wang
authors.forename: Lie-Hang
authors.initials: LH
authors.lastname: Shen
mesh_terms: D001798:Blood Proteins / Q000378:metabolism*; D002846:Chromatography, Affinity; D002850:Chromatography, Gel; D002951:Citrates / Q000378:metabolism*; D005260:Female; D005708:Gallium / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011485:Protein Binding; D019783:Technetium Tc 99m Dimercaptosuccinic Acid / Q000378:metabolism*; D013696:Temperature; D014168:Transferrin / Q000378:metabolism
chemical_list: D001798:Blood Proteins; D002951:Citrates; D014168:Transferrin; D019783:Technetium Tc 99m Dimercaptosuccinic Acid; D005708:Gallium; C103850:gallium citrate