PSMA-Targeted Polygadolinium Clusters: A Novel Agent for Imaging Prostate Cancer
Abstract
Controlled hydrolysis of lanthanide element or yttrium salts in the presence of amino acids yields a series of polynuclear clusters with two four twelve fourteen and fifteen lanthanide or yttrium centers bridged by hydroxides and possessing chelating amino acids. The MRI relaxivity of the gadolinium (Gd) clusters has been studied in vitro with an unprecedented large pH-dependent value of 165 mM-1 s-1 for the Gd14 cluster. We have crystallized dysprosium (Dy) analogs of the dinuclear and tetranuclear clusters for neutron diffraction analysis in order to determine the dysprosium...hydrogen (hydroxide) distance. Yttrium analogs have been prepared structurally characterized and studied by yttrium-89 NMR spectroscopy in order to determine solution structures. The first attempt at preparing a Y15 cluster gave in the presence of residual carbonate an unprecedented Y60 polyhedral cluster that suggest routes to larger Gd clusters. Europium (Eu) cluster analogs have been prepared and their reduction explored in order to exploit the Eu(ll)-Eu(lll) redox couple and develop a redox-sensitive MRl reporter for reactive oxygen species in tumors. A potentially multinuclear chelating ligand with amino acid serine moieties at each end has been prepared by multi-step organic synthesis for ditopic coordination of the Gd14 cluster.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 2008
- Accession Number
- ADA483731
Entities
People
- Louis Messerle
Organizations
- University of Iowa