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Is DTPA a good competing chelating agent for Th(IV) in human serum and suitable in targeted alpha therapy?
Le Du A., Sabatie A., Montavon G., Morgenstern A.
Journal of Inorganic Biochemistry 109 (2012) 82-89 - http://hal.in2p3.fr/in2p3-00677678
Is DTPA a good competing chelating agent for Th(IV) in human serum and suitable in targeted alpha therapy?
A. Le Du1, A. Sabatie1, Gilles Montavon1, 2, A. Morgenstern
1 :  SUBATECH - Laboratoire SUBATECH Nantes
CNRS : UMR6457 – IN2P3 – Université de Nantes – École Nationale Supérieure des Mines - Nantes
4, rue Alfred Kastler - 44070 Nantes Cedex 03
2 :  EM NANTES - École nationale supérieure des Mines de Nantes
École Nationale Supérieure des Mines - Nantes
La Chantrerie - 4, rue Alfred Kastler - BP 20722 - 44307 Nantes cedex 3
The interaction between thorium and human serum components was studied using difference ultraviolet spectroscopy (DUS), ultrafiltration and high-pressure-anion exchange chromatography (HPAEC) with external inductively conducted plasma mass spectrometry (ICP-MS) analysis. Experimental data are compared with modelling results based on the law of mass action. Human serum transferrin (HSTf) interacts strongly with Th(IV), forming a ternary complex including two synergistic carbonate anions. This complex governs Th(IV) speciation under blood serum conditions. Considering the generally used Langmuir-type model, values of 1033.5 and 1032.5 were obtained for strong and weak sites, respectively. We showed that trace amounts of diethylene triamine pentaacetic acid (DTPA) cannot complex Th(IV) in the blood serum at equilibrium. Unexpectedly this effect is not related to the competition with HSTf but is due to the strong competition with major divalent metal ions for DTPA. However, Th-DTPA complex was shown to be stable for a few hours when it is formed before addition in the biological medium; this is related to the high kinetic stability of the complex. This makes DTPA a potential chelating agent for synthesis of 226Th-labeled biomolecules for application in targeted alpha therapy.

Articles dans des revues avec comité de lecture
Journal of Inorganic Biochemistry (J Inorg Biochem)
Publisher Elsevier
ISSN 0162-0134 

Thorium Targeted alpha therapy Speciation Transferrin DTPA
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