99mTc-hydroxypropyl-b-cyclodextrin: possible role in infection imaging

Introduction and Purpose: The X-ray crystallography at 2.3 A resolutions demonstrated, maltose-binding protein over bacterial membrane as a primary periplasmic receptor for maltose, which is also responsible for active transport and chemotaxis. Moreover the binding of cyclodextrin (cyclomaltoheptose), dextrin and other oligosaccharide derivatives to maltose binding protein from Escherichia coli, Streptococcus pneumoniae etc. using X-ray crystallography techniques has also been reported. Molecular interaction between host mucosal surfaces and outer membrane components of microbes is crucial in the infection process. In the initiation of any bacterial infection, basically the bacteria on contact encounter with mucosal epithelial barrier of the human host. After bacterial adherence, the epithelial cells initiate a non-specific or innate immune response by producing proinflammatory factors. The adherences of bacteria to human cells are mediated by bacterial lectins. The subsequent inflammatory response to bacterial infections can be utilized in detection and /or elimination of invading microorganism. Hydroxypropyl-β-cyclodextrin is a class of non-reducing oligosaccharide consisting of seven glucose monomers joined together through glycosidic linkages has been used extensively in human drug formulations. Moreover the presence of free hydroxyl groups is also essential for cyclodextrin metabolism in periplasmic and cytoplasmic spaces, aerobically and also anaerobically. This also suggest that the transport of these molecules through outer and inner membranes of Gram -ve and gram +ve bacteria. With this background we labeled hydroxypropyl-β-cyclodextrin with 99mTcO4 and after proper quality control procedures we used 99mTc labeled cyclodextrin for infection imaging in patients having positive documented clinical findings and infected sites. Methods: The labeling of Hydroxypropyl-β-cyclodextrin derivative was done by stannous chloride reduction method using freshly eluted 99mTcO4 from Amarsham 99Mo-99mTc generator. The quality control procedures were followed. The assessment of radiopharmaceutical purity was evaluated using ITLC. The Images were taken at different time intervals for evaluation. We also compared our results using different radiopharmaceuticals. Results: The labeling efficiency 99mTc to β- cyclodextrin was more than 99%. Increased uptakes of labeled B-cyclodextrin in infected areas in three different cases were observed. The biopsies taken from the infected sites also confirmed our findings. The findings are comparable with 99mTc labeled leukocyte, 99mTc MDP and 99mTc(V) DMSA images. The time interval for delayed images is also less compared to WBC, MDP and DMSA imaging time. Conclusion: Our results confirm the accumulation of 99mTc-hydroxypropyl-β- cyclodextrin in infected areas and the early images obtained can also be taken as positive sign. The labeling procedure is cheaper; less cumbersome and early images are comparable with other imaging modalities. The localization of 99mTc hydroxypropyl-β-cyclodextrin may be possibly due to either its binding to sialoprotein perplasmic receptors or the maltose binding proteins present on gram + ve or gram -ve bacterial membrane as reported in the literature. (authors)