Abstract(s) :

(Anglais) Introduction Ga-complexes are invaluable tools as probes for imaging studies with 66Ga, 67Ga, or 68Ga radiopharmaceuticals, and as therapeutic agents for the treatment of a number of cancer and infectious diseases with non-radioactive gallium compounds [1]. While an absence of free Ga3+ ions is mandatory in the context of Ga-complexes for radiodiagnostic, their presence seems to be a key factor for the therapeutic efficacy of gallium agents because free Ga3+ ions tend to form Ga-transferrin complexes or [Ga(OH)4]- in vivo [2, 3]. In either case, Ga-complexes should thus be carefully checked for the presence of free gallium ions before use. 71Ga NMR could be an interesting technique to rapidly detect the presence of these undesirable ions in solutions of Ga-complexes. Results and discussion 71Ga NMR is less spread among the liquid NMR community, the main cause being probably the broad peaks generally exhibited. 71Ga is indeed a nucleus of spin 3/2 with a large quadrupolar moment of 0.112 x 10-28 m2 [4]. Only resonances of Ga in a highly symmetrical local environment are sharp enough to be detected [5]. Free gallium ions can however be detected at acidic pH as [Ga(H2O)6]3+ and at neutral or basic pH as [Ga(OH)4]- [2, 6]. In a preliminary study, a solution of Ga-DOTA 50 mM at pH 7.5 containing free gallium ions has been studied. Two peaks were observed on the 71Ga NMR spectra, a larger one at around 137 ppm which corresponds to gallium incorporated in the complex and a sharper one at 223 ppm corresponding to free gallium in the form of [Ga(OH)4]-. The chemical shifts are expressed with respect to the absorption of an external reference composed of Ga(NO3)3 at acidic pH. The influence of viscosity on the 71Ga NMR spectra of Ga-DOTA has also been studied and, as expected, the resonance of Ga broadens with the increase of the viscosity of the solution. This confirms the possibility of using Ga linewidth to probe the dynamics of molecular imaging probes. Conclusions 71Ga NMR signals are very sensitive to the local environment and dynamics of the nucleus such as the pH, the viscosity and the symmetry. In this preliminary work, we have shown that 71Ga NMR could be a useful tool to rapidly detect the presence of free gallium ions in solutions of Ga-complexes. References (1) Bandoli, G.; Dolmella, A.; Tisato, F.; Porchia, M.; Refosco, F. Coord. Chem. Rev. 2009, 253, 56-77. (2) Aramini, J. M.; Mcintyre, D. D.; Vogel, H. J. J. Am. Chem. Soc. 1994, 116, 11506-11511. (3) Akitt, J. W.; Kettle, D. Magn. Reson. Chem. 1989, 27, 377-379. (4) Andre, J. P.; Macke, H. R. J. Inorg. Biochem. 2003, 97, 315-323. (5) Glickson, J. D.; Pitner, T. P.; Webb, J.; Gams, R. A. J. Am. Chem. Soc. 1975, 97, 1679-1683. (6) Garcia, R.; Fouskova, P.; Gano, L.; Paulo, A.; Campello, P.; Toth, E.; Santos, I. J. Biol. Inorg. Chem. 2009, 14, 261-271.