Nuclear Magnetic Resonance (NMR) imaging is a most powerful method for the non-invasive diagnosis of disease. A fundamental limitation of the technique derives from the fact that images are constructed from Tl relaxation time measurements of protons in the various biological """"""""compartments"""""""". If T1 values for differing soft tissue types are similar, the types will not, in general, be resolvable in the images. A potential method for improving this situation is the development of relaxation agents which specifically alter T1 relaxation rates in tissues where they may be concentrated. We have recently shown that metal chelates are useful as an NMR contrast agent in myelography and cisternography. We have prepared a new and superior contrast agent, Gadolinium (Gd)DOTA. This chelate has recently been shown to be more stable in vivo than Gd(DTPA). This year, we report the preparation of new chelating ligands for linkage of contrast agents to proteins. An effective, efficient synthesis of 1-p-nitrobenzyl DOTA has been completed.
