A Use of Modified Cyclodextrins as a Transporter for a Radiolabeled Tracer NMR Investigation

Abstract  Cyclodextrins (D. Duchêne (ed.): New Trends in Cyclodextrins and Derivatives (1991)) have long been shown to be capable of modifying the water solubility of a number of hydrophobic guests through the formation of inclusion complexes. Among the three natural cyclodextrins (α, β and γ-cyclodextrins containing 6, 7 and 8 d-glucopyranose units, respectively), β-cyclodextrin is by far the most commonly used although it exhibits a weaker solubility in water (and therefore a weaker solubilization power). This specific feature has encouraged the synthesis of derivatives exhibiting an increased solubility in water. Methylated cyclodextrins are amongst the simplest derivatives, and their properties regarding the solubility and the solubilization power for hydrophobic guests are well documented especially concerning Heptakis (2,6-di-Omethyl)-cyclodextrin (DIMEB) and Heptakis (2,3,6-tri-Omethyl)-cyclodextrin (TRIMEB) K. Koizumi et al.:J. Chromatogr. 368, 329–337 (1986). In order to avoid the use of human serum albumin (HSA), this property has been applied here to the solubilization of a very sparingly water-soluble fatty acid derivative (16-iodo-3-methylhexadecanoic acid), which is known to localise in viable myocardial cells, allowing the generation of functional images reflecting the viability of the cardiac tissue through the use of radiolabeled analog (Demaison et al.: J. Nucl-Med. 29, 1230–1236 (1998)). Nuclear magnetic resonance (NMR) was used throughout this study to evidence that the observed solubilization and stabilisation (under conditions required for sterilisation) induced by cyclodextrins are due to the formation of a true inclusion complex and not to non-specific interactions; This technique further allows to derive thermodynamic as well as structural informations for this complex. On one hand, the inclusion complex prevents thermal degradation during sterilisation process compared to HSA. On the other hand, NMR displacement experiments against HSA showed that the complex likely dissociates in vivo.