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|Title:||Is DTPA a good competing chelating agent for Th(IV) in human serum and suitable in targeted alpha therapy?|
|Authors:||LE DU Alicia; SABATIE-GEGOVA Andrea; MORGENSTERN Alfred; MONTAVON Gilles|
|Citation:||JOURNAL OF INORGANIC BIOCHEMISTRY vol. 109 p. 82 - 89|
|Publisher:||ELSEVIER SCIENCE INC|
|Type:||Articles in periodicals and books|
|Abstract:||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 coupled plasma mass spectrometry (ICP–MS) analysis. Experimental data are compared with modelling results based on the law of mass action. Transferrin 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 carrying Th-226 in the body for targeted alpha therapy applications.|
|JRC Institute:||Nuclear Safety and Security|
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