Multilanthanide Systems for Medical Imaging Applications

Abstract

Molecules containing multiple lanthanide ions have unique potential in applications for medical imaging including the areas of magnetic resonance imaging (MRI) and fluoresence imaging. The study of multilanthanide complexes as contrast agents for MRI and as biologically responsive fluorescent probes has resulted in an improved understanding of the structural characteristics that govern the behavior of these complexes. This review will survey the last five years of progress in multinuclear lanthanide complexes with a specific focus on the structural parameters that impact potential medical imaging applications. The patents cited in this review are from the last five years and describe contrast agents that contain multiple lanthanide ions.

Enhancing PET Signal at Target Tissue in Vivo: Dendritic and Multimeric Tris(hydroxypyridinone) Conjugates for Molecular Imaging of αvβ3 Integrin Expression with Gallium-68

“…Dendritic and multimeric chelator systems for coordination of Gd 3+ and lanthanides provide enhanced contrast as MRI agents compared to their single-chelator counterparts, in large part due to the increased number of metal complexes present. − Multimeric constructs containing multiple chelating groups (including hydroxypyridinones) have also been synthesized for the purposes of sequestering trace metal ions. , A small body of work has been described in which the number of radiometal coordination sites on a radiolabeled protein/antibody has been increased by incorporation of either a dendrimer possessing multiple chelating groups, − or a pendant function (such as polylysine) on which multiple chelators are appended. − In these cases, the functionalized/radiolabeled biomolecule retained affinity for receptor targets in vitro ,, and in vivo. ,,, Additionally, when compared to bioconjugates containing fewer chelating groups, dendrimer or multichelator conjugated proteins demonstrated higher specific activitythat is, a higher number of radionuclides were bound per bioconjugate compared to homologues containing a single chelator. ,− In some cases, this resulted in higher concentrations of radioactivity at target tissue (tumors) in vivo …”

Concentration-Independent pH Detection with a Luminescent Dimetallic Eu(III)-Based Probe

“…Reports describing time-resolved microscopy, luminescence-lifetime imaging, and phosphorescence-quenching microscopy demonstrate that luminescence-decay rates can be determined from microscopy and are, therefore, a useful parameter for sensing applications. Lanthanide-based probes often exhibit low sensitivity that can be addressed by the use of antennae or through he use of multimetallic complexes that increase sensitivity additively . In targeting the multimetallic strategy, we synthesized a new dimetallic Eu(III)-containing complex, 1 , that responds to pH over a physiologically relevant range of 4–8 by a new mechanism, based on luminescence-decay rates, that is independent of the probe concentration and selective for only proton concentration.…”