Spin Labeled Bovine Serum Albumin, Spin Labeled Bovine Serum Albumin Chelating Agents and Their Gadolinium Complexes. Potential Contrast Enhancing Agents for Magnetic Resonance Imaging

Abstract

Abstract Bovine Serum Albumin (BSA) was spin labeled using the active esters 3 and 5 containing a nitroxyl radical to give the spin labeled BSA derivatives 4 and 6. Spin labeled C D TA , DTPA and TTHA chelating agents 10, 13 and 16 and the corresponding BSA derivatives 17, 18 and 19 and their gadolinium complexes 20, 21 and 22 were synthesized. All these BSA derivatives were evaluated as possible contrast enhancing agents for NMR imaging by measurement of spin-lattice (T1) and spin-spin (T2) relaxations and by calculations of relaxivities i.e., slopes of 1/T1 versus concentration plots. The spin labeled BSA-complexon-gadolinium conjugates 20, 21 and 22 were found to have better relaxation times and relaxivities than the BSA spin labeled derivatives 4, 6, 17, 18 and 19. The spin count for the BSA derivatives 4, 6, 17, 18 and 19 and for their gadolinium conjugates 20, 21 and 22 was found to be between 9 -1 0 spins/molecule of the protein. The gadolinium conjugates 20, 21 and 22 of spin labeled BSA possess high relaxivities combined with a nitroxyl marker that could be used with EPR to assess pharmacokinetic behaviors of these potential contrast agents