FLUORESCENTLY DETECTABLE MAGNETIC-RESONANCE-IMAGING AGENTS

This report describes the synthesis, characterization, and in vivo tes ting of several bifunctional contrast-enhancing agents for optical and magnetic resonance imaging (MRI) of experimental animals. These new a gents integrate the advantages of both techniques since they can be vi sualized simultaneously by light and MRI microscopy. Employing this st rategy allows the same biological structures of a specimen to be studi ed at dramatically different resolutions and depths. The complexes pos sess a metal chelator for binding a paramagnetic ion, gadolinium (Gd3), and a covalently attached fluorescent dye. The first class of compl exes are low-molecular weight species that are composed of the macrocy clic tetraamine 10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic aci d (DOTA) as the metal-chelating Ligand coupled to tetramethylrhodamine . The second class of MRI-enhancing agents are composed of high-molecu lar weight polymers that are membrane impermeable and once injected in to a cell or cells are trapped inside. These complexes possess multipl e copies of both the metal-chelator-diethylenetriaminepentaacetic acid (DTPA) and the tetramethylrhodamine attached to a macromolecular fram ework of either poly(D-lysine) (pdl) or dextran. Images acquired of si ngle cells after injection with these bifunctional agents enabled us t o follow the relative motions and reorganizations of different cell la yers during amphibian gastrulation and neurulation in Xenopus laevis e mbryos.