Gadolinium Complex of 1,4,7,10-Tetraazacyclododecane-1,4,7-trisacetic acid (DO3A) Conjugate of [(p-aniline benzothiazole)methyl]pyridine as a Tumor-Targeting MRI Contrast Agent

Abstract

The synthesis of a DO3A conjugate of [(p-aniline benzothiazole)methyl]pyridine (<TEX>$L^2H_3$</TEX>) and its gadolinium complex of the type [<TEX>$Gd(L^2)(H_2O)$</TEX>] (<TEX>$GdL^2$</TEX>) is described. The <TEX>$R_1$</TEX> relaxivity (<TEX>$=4.50mM^{-1}sec^{-1}$</TEX>) and kinetic inertness of <TEX>$GdL^2$</TEX> compares well with those of structurally analogous Dotarem<TEX>$^{(R)}$</TEX> (<TEX>$R_1=3.70mM^{-1}sec^{-1}$</TEX>), a typical extracellular (ECF) MRI contrast agent (CA). Yet, by comparison with Dotarem<TEX>$^{(R)}$</TEX>, <TEX>$GdL^2$</TEX> exhibits non-covalent interactions with human serum albumin (HSA) as evidenced by the <TEX>${\varepsilon}^*$</TEX> titration curve along with in vivo MR signal enhancement in both aorta and heart. Liver-specific nature of <TEX>$GdL^2$</TEX> is also observed as excretion is made through gallbladder. Most notably, <TEX>$GdL^2$</TEX> further demonstrates specificity toward the MDA-MB-231 breast cancer.