[en] ^99mTc(V) Dimercaptosuccinic acid (DMSA), a well known tumor seeking agent, has been well documented. The attachment of a β-emitter /higher energy γ- emitter in lieu of Tc-99m .in its position. DMSA (labeled/unlabeled) loaded polymeric microspheric delivery system may be utilized theoretically as therapeutic agent for neurogenic/neuroendocrine tumors and some other types of tumors. The aim of our studies was to deliver the loaded drug to tumors and to irradiate the tumor tissue for the extended period. The bioabsorbable poly lactic-co-glycolic acid (75:25) microspheres ranging between 200 nm-2.00 μm were developed using double emulsion solvent evaporation method. The known amount of dimercaptosuccinic acid was loaded and tagged with freshly prepared Re-188 eluted from W-188 Generator. For microsphere characterization unlabelled and ^99mTc(V) DMSA labeled microspheres were also prepared. Microspheres of different sizes were prepared. Size and morphology was studied by SEM. Drug (labeled/unlabeled DMSA) loading was dependent on the size of microspheres. In vitro drug loading and drug release was recorded. Thermal analysis demonstrated that the drug inside the microspheres was amorphous crystalline state, as melting endothermic peak of DMSA could not be detected in the drug loaded microspheres. The morphology based glioma cell kinetics using electron microscopy, demonstrated the in-vitro ability of radiolabelled DMSA to enter within the cell and block the cell growth; potentially by enhancing the radiation doses to cultured cells, when incubated with a microsphere-based drug delivery system.

[en] A protein synthesis marker ¹¹C-methionine-PET was used in differentiating residual post-radiotherapeutic viability and to differentiate the low-grade proliferating glioma with glioblastoma, SPECT facility has wider availability and reports with ²⁰¹Thallium indicated that it can differentiate recurrence from necrosis. Since 11C and 201Thallium are cyclotron produced isotopes and in underdeveloped / developing countries, non-availability of cyclotron, PET cameras and their costing are the main constraints. With this aim studies were undertaken to label Methionine with technetium-99m for its possible use in brain tumor imaging. The l, methionine, was labeled with Technetium-99m after modifiying certain steps as reported by Tubis et al, and also by transchelating using a weak prochelator glucoheptonate. The labeling efficiencies were in order of 99 % and 97 % with chelating and transchelating mehods. In our studies we found that Tc-99m Methionine SPECT images are comparable with ¹¹C - methionine PET images. The Methionine uptake index was calculated by drawing ROI around the tumor in the slice showing maximum activity and obtaining the counts. To know the background counts a similar ROI was drawn on the contra lateral side/lobe. The ratio of the two was obtained. The ratio as calculated in order of 6.0 and 8.2 for higher grade and low-grade glioma, respectively. The studies conducted so far in 150 patients indicated that this technology could be utilized further to (a) grading gliomas and (b) differentiating glioma from non-tumoral lesions and radiation necrosis.

[en] 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)

[en] The present study was designed to unravel the bioevaluation of [^99mTc]Tc-GSH in HT 29 colon cancer cell line as well as in experimentally induced colon cancer. The radiochemical yield was observed to be 95.93 ± 1.09%. In silico docking studies revealed that [^99mTc]Tc-GSH gets well accommodated in the binding pocket of gamma-glutamyl transpeptidase in comparable orientation with lowest estimated binding energy - 81.90. Toxicity assays i.e. 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide and trypan blue exclusion assay showed that radiocomplex is non-toxic to HT 29 cells. In conclusion, in vitro and in vivo results indicated the [^99mTc]Tc-GSH radiocomplex has tumor delineating features and also exhibits selectivity for colon tumor. (author)