Sialic acid plays a central role in many physiologic and pathologic processes. It is a key recognition site that allows the differentiation between Avianinfluenzaand humaninfluenza. It is an essential component of gangliosides that are particularly abundant in neural tissue and of polysialic acid (PSA) that modify neural cell adhesion molecules that are important in neonatal brain development. In the chemical exchange saturation transfer (CEST) NMR method changes of the water signal upon irradiation of exchangeable protons such as amide, amide and hydroxyl are monitored. It enables to detect low concentrations of endogenous or exogenous cellular components. Sialic acid with its 6 exchangeable protons, as well as PSA are good candidates for CEST NMR detection. Using selective TOCSY measurements of sialic acid we have assigned the signals at 1.7, 1.2, 0.75 and 0.55 ppm upfield to the water, to hydroxyls at positions 2,4, 8 and 9 respectively. These signals are sharpest around pH 6.2 and are broadened at higher and at lower pH values. The CEST experiment for a solution of 300mM sialic acid, pH 6.7, 250C as a function of strength the irradiation field (B1) is given in Fig. 1. . The PSA was obtained from meningitis-causing bacteria. It is a linear homo-polymer with a length of approximately 200 sialic residues. The linkage is between the OH residues on C2 and C8. For a solution of PSA with a concentration corresponding to 20mM sialic acid residues at neutral pH, 360C very significant CEST effects were obtained with B1 fields of 47-94 Hz. (Fig. 2) In conclusion: The significant CEST results for sialic and polysialic acids indicate that SialoCEST has the potential for imaging these compounds in vivo.
Fig. 1 Fig. 2
