Is DTPA a good competing chelating agent for Th(IV) in human serum and suitable in targeted alpha therapy? - Université de Nantes Accéder directement au contenu
Article Dans Une Revue Journal of Inorganic Biochemistry Année : 2012

Is DTPA a good competing chelating agent for Th(IV) in human serum and suitable in targeted alpha therapy?

Gilles F Montavon
A. Morgenstern

Résumé

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.

Domaines

Radiochimie
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Dates et versions

in2p3-00677678 , version 1 (09-03-2012)

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Citer

A. Le Du, A. Sabatie, Gilles F Montavon, A. Morgenstern. Is DTPA a good competing chelating agent for Th(IV) in human serum and suitable in targeted alpha therapy?. Journal of Inorganic Biochemistry, 2012, 109, pp.82-89. ⟨10.1016/j.jinorgbio.2011.12.011⟩. ⟨in2p3-00677678⟩
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