Bile acids at work : Development of a new intravascular MRI contrast agent

Complexes of Gd(III) featuring strong binding to human serum albumin (HSA) can be potentially used as intravascular MRI contrast agents. Accordingly, a series of Gd(III) complexes containing a bile acid moiety as the HSA binding subunit were synthesised. Diethylenetriaminepentaacetic acid was used as the chelating moiety of Gd(III) ion for all the conjugates. Derivatives of cholic, chenodeoxycholic, deoxycholic, and lithocholic acids, as well as bile acids in which the 12-α OH group was oxidized to a ketone, were prepared. Preliminary screening, which was based on the evaluation of binding to HSA and in vivo tolerability (in mice), led to the identification of the conjugate containing a deoxycholic subunit (i.e. 1c) as the clinical candidate. During development, the route to 1c used for the research phase was largely modified, taking advantage of a different synthetic approach.