TY - JOUR
T1 - Evaluation of Tc-99m (V) DMSA binding to human plasma proteins
AU - Lee, Bi Fang
AU - Yeh, Jwu Lai
AU - Chiu, Nan Tsing
AU - Liu, Gin Chung
AU - Yu, Hsin Su
AU - Wang, Mei Hui
AU - Shen, Lie Hang
N1 - Funding Information:
We thank Chin-Ling Chu for statistical advice, Bi-Ing Chang for assistance with affinity chromatography, and Gang Ting and Shiaw-Pyng Wey for helpful discussions on experimental design. We also thank Hui-Ling Lee for secretarial help. This work was supported in part by grants from the National Science Council of Taiwan (NSC-89-2314-B-006-233-M08, NSC-90-2314-B-006-146, NSC-90-NU-7-006-006 and NSC91-NU-7-006-001).
PY - 2008/1
Y1 - 2008/1
N2 - 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°C and another at 37°C) 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°C and 73-80% at 4°C. The figures for Ga-67 citrate were 43-53% at 37°C and 75-81% at 4°C. Electrophoresis showed that Tc-99m (V) DMSA was mostly bound to plasma albumin (36.05 ± 2.48% at 37°C and 60.04 ± 1.87% at 4°C), and that the proportion of Ga-67 radioactivity associated with β-globulin was 34.23 ± 1.37% at 37°C and 55.71 ± 3.69% at 4°C. 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.
AB - 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°C and another at 37°C) 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°C and 73-80% at 4°C. The figures for Ga-67 citrate were 43-53% at 37°C and 75-81% at 4°C. Electrophoresis showed that Tc-99m (V) DMSA was mostly bound to plasma albumin (36.05 ± 2.48% at 37°C and 60.04 ± 1.87% at 4°C), and that the proportion of Ga-67 radioactivity associated with β-globulin was 34.23 ± 1.37% at 37°C and 55.71 ± 3.69% at 4°C. 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.
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U2 - 10.1016/S1607-551X(08)70066-4
DO - 10.1016/S1607-551X(08)70066-4
M3 - Article
C2 - 18218563
AN - SCOPUS:39649103398
VL - 24
SP - 1
EP - 9
JO - Kaohsiung Journal of Medical Sciences
JF - Kaohsiung Journal of Medical Sciences
SN - 1607-551X
IS - 1
ER -