MR imaging and spectroscopy applications of lanthanide complexes with macrocyclic phosphonate and phosphonate ester ligands

Abstract

Ligands derived from the macrocycle, 1,4,7,10-tetraazacyclododecane, with differing side-chain chelating arms form complexes with the bivalent lanthanide cations that are both thermodynamically stable and kinetically inert. This short review article is intended to introduce the reader to a few potential biomedical applications of various lanthanide complexes formed with macrocyclic ligands derived from the cyclen. TmDOTP5- has proven to be quite useful as a NMR shift reagent (SR) for biological cations, capable of resolving intra- and extracellular 23Na signals in the in vivo rat kidney, liver, heart and skeletal muscle. Lanthanide complexes of the monoester derivatives of DOTP have lower net charge and differing hydrophobicities, depending upon the length of the alkyl sidechains. These complexes are handled differently in rats, with the tetra(ethyl ester) complexes clearing via renal excretion and the tetra(n-butyl ester) complexes via biliary excretion. The tetra(trifluoroethyl ester) complexes are handled more like the n-butyl ester complexes than the ethyl ester complexes. High resolution 19F NMR spectra of the latter complexes reveal that six diastereomers are present in solution at nearly equal concentrations.