The solution equilibria, acid dissociation, and serum stability of a series of Y(III) complexes of DTPA ligands functionalized with p-nitrobenzyl, methyl, and trans-cyclohexyl substituents were studied. The thermodynamic stability of the complexes studied ranged from log K = 21.53 to 24.7. Acid dissociation rates were found to decrease as the substitution on the carbon backbone increased, and significant differences in dissociation rates were observed for the Y(III) complexes of a pair of diasteriomeric cyclohexyl-DTPA ligands. While one diastereomer was found to have the slowest acid dissociation rate of the entire DTPA series, it was remarkably labile in both serum stability and in vivo studies.