| The current generation of contrast agents available or under development for clinical magnetic resonance imaging (MRI) consist mainly of gadolinium complexes of acyclic and macrocyclic aminopolycarboxylates, aminopolyphisphonates, and aminopolyphosphinates. Improved contrast agents will require complexes which can remain in the body longer and/or be targeted toward specific tissues. The new bifunctional ligand DTPA-bis-(glucosamide), or (DTPA-BGAM) has been synthesized as a step toward preparing ligands capable of delivering either magneto- (gadolinium) or radio-{dollar}rm(sp{lcub}111{rcub}In){dollar} pharmaceutically relevant metals to glucose receptor sites in vivo. This type of bifunctional agent could be employed in bridging the existing clinical gap between the positron emitting radionuclide based metabolic imaging technologies (in particular, {dollar}sp{lcub}18{rcub}{dollar}F-fluorodeoxyglucose PET) and the more cost effective MRI based imaging technology (which is limited by its inability to provide direct information concerning in vivo metabolic function. vskip162pt; Details of the DTPA-BGAM ligand synthesis and its characterization by conventional analytical techniques (NMR, FTIR, HPLC, ESI-MS) are discussed. In addition, the solution and solid state structures of the various lanthanide (Ln) complexes of DTPA-BGAM as probed using a variety of techniques including potentiometry, proton relaxometry, NMR, and solid and solution state Eu(III) laser luminescence and their roles in evaluating these complexes as potential MRI contrast agents are discussed. Finally, the results concerning the efficacy of these chelates in targeting glucose receptors in Sprague-Dawley rats (as evaluated using the {dollar}rmsp{lcub}111{rcub}In(DTPA{dollar}-BGAM) and {dollar}rmsp{lcub}153{rcub}Gd(DTPA{dollar}-BGAM) radiolabeled complexes) are presented. |
