Indium, transferrin binding

In spite of its larger size, with an ionic radius of 0.80A (161), In3+ appears to bind to transferrin with an affinity close to that of Fe3+ (145). In3+ displaces Cu2+ from copper-saturated ovotransferrin, and the In3+ even remains bound in the presence of an added twofold excess of Fe3+. Indium-transferrin also migrates indistinguishably from iron-transferrin (145) and gives the same closed conformation, as judged by small-angle X-ray scattering (105). 

A further prerequisite for an indium complex to be useful for nuclear medicine applications is that it be resistant to exchange with the plasma protein transferrin. Indium binds to transferrin at the Fe binding site with a stability constant (/f ) of lO in the presence of bicarbonate [7]. The formation constants of indium with ethylenediaminetetraacetic acid (EDTA) (log = 25.0) and DTPA (log Ki = 29.0) are such that at infinite dilution equilibrium would favor the formation of indium transferrin [8J. The slow dissociation of indium from these complexes hinders the formation of indium transferrin. 

The similarities between Ga, In and Fe " are manifest in vivo by the binding of all three ions to the serum protein transferrin, Tf, normally used for iron transpQit. The formation constant for the Ga -Tf complex has been found to be and Welch has calculated values for the equilibrium constants for the exchange of trivalent metal ions between EDTA or DTPA and Tf as shown in Table 19. These figures show that only the DTPA complex of Ga is stable with respect to metal exchange with Tf. Table 19 also shows values for the equilibrium exchange reaction between Tf and hydroxide ion. These indicate that, while the indium-Tf complex should be stable to hydrolysis in vivo, in the long term the insoluble Ga(OH)3 should form from the... 

Hosain E, McIntyre PA, Poulose K, Stern HS and Wagner NH (1969) Binding of trace amounts of ionic indium-113m to plasma transferrin. Clin Chim Acta 24 69-75. 

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