[en] 99mTc(V) Dimercaptosuccinic acid (DMSA) has been well documented as a well-known tumor-seeking agent .The attachment of a b-emitter / higher energy gamma - emitter in lieu of positioned Tc-99m of DMSA molecule, loaded in a polymeric microspheric delivery system may be utilized theoretically as therapeutic agent for neurogenic and neuroendocrine tumors. With this aim studies were conducted using bioabsorbable poly lactic -co glycolic acid (75:25), biocompatible polymer was synthesized and designed in the form of microspheres to degrade slowly over period of several weeks. The synthesized polymeric micro spheres were further loaded with 188Re tagged dimercaptosuccinic acid. A solvent evaporation technique was employed to encapsulate DMSA in PLGA micro spheres. Drug loading and polymeric characterization were initially evaluated using spectophotometric analysis, Thermo gravimetric analysis, and differential scanning calorimetric and infrared spectroscopy. Drug release kinetics indicated that the total amount of DMSA released and the release rate were directly dependent on loading percentage. Radiolabelling efficiency of the tagged polymer was calculated after running the ITLC in Methyl ethyl ketone solvent system. The cold and Re-188 labeled DMSA- PLGA polymeric micro spheres were incubated separately with human Glioma cells in cultured medium for the assessment of its in-vitro kinetics on cell lines. The presence of microspheres nearer to its action sites on cultured glioma cells were demonstrated using scanning electron microscopy

[en] The alpha mercaptopropionyl-glycine, a radio protective chemical, formed due to condensation of peptide linkage of thiolactic acid and glycine, have multifunctional effectiveness for wide range of diseases such as liver diseases, skin disease and so on.It is capable of liberating, sulphydryl group (-SH), which has an important function in the human body as an antitoxic agent. The Alpha-mercaptopropionyl glycine was tagged with Technetium-99m in presence and in absence of stannous chloride at pH 6.0 and 7.5 respectively. The efficacy of Technetium-99m binding to Alpha-MPG was compared under different experimental conditions. Gamma-imaging and biodistribution studies were carried out with Technetium-99m labelled alpha-MPG in rabbit and rat model. The presence of mercapto and carboxyl group of the compound essentially formed the chelates and rendered it to behave as a hepatobiliary agent. The absence of Lyophilic bond did not increase the renal excretion at pH 7.5.The scintigraphic and biodistribution studies at pH 7.5 showed its quick clearance from the blood and thereby rapid uptake by hepatic cells and excreted via biliary passage in to the gastrointestinal tract, while at pH 6.0 the excretion through kidneys was maximum. Thus the hepatobiliary properties of the compound was pH dependent. The shift in absorption maxima of the Tc-99m labeled Alpha-MPG to 600 nm was noticed at pH 7.5

[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] Uptake of testosterone-7-³H and estradiol-17β-6,7-³H by various tissues and the effect of testosterone and estradiol-17β on the spermatozoa and accessory genital organs of castrated male rats were studied. The results indicated that there were differences in response of the epididymis and vas deferens to androgen and estrogen. (M.G.B.)

[en] The objective of this article is to critically analyse from the macroeconomics point of view the true picture of private investment in nuclear medicine i.e. whether it is a profit making or loss incurring investment

[en] The melanoma originates from the melanocytes, which are embryologically derived from neural crest. The melanoma of choroids in adults is a very common type primary ocular malignancy, where the tyrosine, an immediate precursor common for both melanin and thyroid hormone synthesis is involved. The neurogenic origins of melanoma and medullary thyroid carcinoma have also been shown to have certain common metabolites, receptors and the receptor binding proteins. Several radiolabelled derivatives either in the form of melanin metabolites or melanin binding agents including receptors/ receptor-binding proteins like somatostatin, calcitonin and other monoclonal antibodies, protein receptors (S-100, myelin basic protein, Leu-7, glial fibrillary acidic protein, HMB-45) etc. have been tried to evaluate/diagnose melanoma, staging or post therapeutic effects. However their cost of production, tedious synthetic and radiolabelling processes and the availability of certain cyclotron produced isotopes were not favorable or patient friendly. Moreover post-therapeutic assessments in melanoma patients were not encouraging. Because of the chelating properties of Tc-99m (V) Dimercaptosuccinic acid with Calcium ion, uptake by neurogenic tumors including ocular retinoblastoma, medullary thyroid carcinoma, pituitary adenoma etc has been demonstrated. Since MTC and Melanoma have the common neural crest origin and producing some common metabolites, receptors/receptor proteins and at the same time Tc-99m (V) DMSA was used in pre and post therapeutic assessment of Medullary thyroid carcinoma extensively. We therefore decided to use Tc-99m (v) DMSA for the assessment of melanoma developed in thyrotoxicosis patients who underwent radioiodine therapy more than 15 years back. The DMSA kits were prepared locally and labeled with Tecnetium-99m at pentavalent state. After the quality control each patients were injected a dose of 10mCi of Tc-99m labeled DMSA.The whole body images were taken after two hrs and the images were analyzed for the accumulation of radiopharmaceutical. Our findings confirmed the accumulation of Tc-99m (V) DMSA in ocular melanoma sites and were comparable with CT images and histochemical findings. Hence this radiopharmaceutical can also be utilized for melanoma imaging. It is cost effective as compared to cyclotron-produced radionuclide and other modalities, where SPECT studies can be repeated and data can be analysed for recurrence and necrosis of melanoma. (authors)

[en] Neurogenic primary or associated secondaries metabolize calcium through different metabolic pathways. Moreover the calcium ions in malignancies play an important role on the spread of metastasis. To assess the extent of spread of malignancy and metastasis a series of calcium-binding proteins have been identified. In addition, the assessment of integrity of staging neurogenic malignancy, and post-therapeutic viability, the calcium ion can also be targeted for diagnosis utilizing various chelating agents. Quantitatively, ultrasonography can detect a neurogenic malignant lesion in a patient earlier than CT, even when calcium ion concentration is low enough, as demonstrated in our studies in abdominal neuroblastoma. However their role to assess functional viability of malignant tumors using ultrasonography, CT and MRI are very much limited. In addition several hydroxyapatite crystal-binding radiopharmaceuticals have been used in nuclear oncology, but most of them were not lesion specific, because of their chemo adsorption by normal bone/tissue having hydroxyapatite mineral. With this aim we conducted our studies in patients with varieties of neurogenic tumors (Optic nerve tumors, Melanoma, Medullary thyroid cancer, Melanoma, Neurogennic carcinoma of urinary bladder, Carcinoid rectum etc.) with Tc-99m (V) Dimercaptosuccinic acid having special affinity for ionic calcium. The DMSA kits were prepared locally and labeled with Tecnetium-99m at pentavalent state. After the quality control each patients were injected a dose of 15-20 mCi of Tc-99m labeled DMSA.The whole body images were taken after two hrs and the images were analyzed for the accumulation of radiopharmaceutical. Our findings confirmed the accumulation of Tc-99m (V) DMSA in neurogenic malignancy sites and were comparable with the Images obtained using other modalities and histochemical findings. The scan can also be utilized for differentiating necrosis from recurrence. The Tc-99m (V) DMSA is cheaper, widely available modality, having good sensitivity and specificity for neurogenic tumors. (authors)

No abstract available

[en] Full text: Aim/Background: Acute gastrointestinal infections due to rotaviruses and other enteric pathogens are major causes of morbidity and mortality in infants and young children throughout the world. The oligosaccharide fraction of human milk bear structural homology to cell surface glycoconjugates and used as receptors by pathogens which protect nursing infants from infections. The similarities between cell surface glycoconjugates and oligosaccharides in human milk strengthen the idea that specific interactions of those oligosaccharides with pathogenic microorganisms do occur preventing the attachment of microbes to epithelial cells. Streptococcus pneumoniae and Haemophilus influenzas are major respiratory pathogens. They attach to the mucosal surfaces of the respiratory tract. This attachment is the first contact with the host tissues and may determine whether the bacteria will colonize the mucosa and cause infection. Conversely, if attachment is inhibited, the infection may be prevented. The free oligosaccharide blocks adhesion. So does human milk, which contains the receptor oligosaccharides. More than 130 lactose-derived oligosaccharides have been identified in human milk. There is the striking evidence that human milk oligosaccharides are potent inhibitors of bacterial adhesion to epithelial surfaces, an initial stage of infective processes. Therefore, these oligosaccharides are considered to be soluble receptor analogues of epithelial cell surfaces participating in the non-immunological defense system of human milk-fed infants. About 130 oligosaccharide complexes have been isolated and characterized from human milk. The presence of oligosaccharides binding proteins (eg.Cym E and Cym B) in bacterial membranes have also been reported. The binding of Streptococcus pneumonia, enteropathogenic E.coli and Haemophilus to their receptors is inhibited by human breast milk oligosaccharides. The binding of oligosaccharides to highly specific recognition receptor molecule lectin is known to be present over bacterial membrane. Maltose binding protein bound to beta-cyclodextrin has two globular domains - how they are oriented in this complex was determined by solution NMR methods based on dipolar coupling measurements. The maltose and β-cyclodextrin binding through residues Asp 41 and Ser 211 are known as MBP backbone. The distance between the C atoms of Asp 41 and Set 211 in the maltose-MBP and β- cyclodextrin-MBP complexes is 15 and 24 A, respectively. The distance between the hydroxyl group of Ser 211 and the carboxyl carbon of Asp 41 in the maltose-MBP and b-cyclodextrin complexes is 11 and 23 A, respectively. The presence of free hydroxyl groups for cyclodextrin metabolism in periplasmic and cytoplasmic spaces, suggested the transport of these molecules through outer and inner membranes of gram -ve and gram +ve bacteria. With this background studies were undertaken to utilize β-cyclodextrin after radio labeling with ^99mTcO₄ as oligosaccharide probe for infection imaging. Methods and materials: The labeling of 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.The Clinical ethical clearance and approval from Drug controller of India was obtained. Results: The labeling efficiency ^99mTcO₄ to β- cyclodextrin was more than 97%. Increased uptakes of labeled β-cyclodextrin in infected areas were visualized in different cases were observed. Discussions: Patients with proven infections, by histopathology, were compared, which confirmed our findings. Some of our cases were compared with ^99mTc labeled leukocyte, ^99mTc MDP and ^99mTc(V) DMSA imaging. Our results confirmed the accumulation of ^99mTc-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. Conclusions: The localization of ^99mTc-β cyclodextrin may be possibly due to either its binding to sialoprotein receptors or the maltose binding proteins present on gram + ve or/and gram -ve bacterial membrane as reported in the literature. (author)

[en] Ocular melanoma in Thyrotoxic patients is a very rare type of cancer, where its exact cause or link between the radiation exposure due to radioiodine therapy or other external radiation exposure on its development is still an unsolved puzzle. In the recent years the ectopic production of melanin and presence of somatostatin receptors in medullary thyroid carcinoma demonstrated its neuroendocrine origin. Thereafter the accumulation of 99mTc (V) Dimercapto succinic acid in medullary thyroid carcinoma cells were also reported. In 1991, Feggi et al demonstrated the scintigraphic uptake of radiolabelled monoclonal antibodies directed against melanoma in follicular thyroid adenoma. On this basis we conducted studies with 99m Tc (V) DMSA, in two thyrotoxic patients, received radioiodine therapy in 1985 and 1986 respectively and developed choroidal melanoma (in one case lacrimal gland was also involved), however the exact etiology was not established. The DMSA cold kits were prepared locally and labeled at five-valent state of ^99m Technetium. Proper quality control methods were applied and the dose of 10 mCi was injected in each patient. The whole body images as well as brain SPECT images were taken after two hrs. and analyzed for further evaluation. The 99mTc(V) DMSA accumulation in melanoma site was seen in SPECT images .Our findings were further confirmed by CT and histochemistry. It further corroborates the neuroendocrine origin of melanoma having originated from the neural crest during development as mentioned in literature