Evaluation Of [11C]MPC-6827 As A Microtubule Targeting Pet Radiotracer In Cancer Cell Lines

Objective: The objective of this study was to evaluate the uptake and specificity of [11C]MPC-6827, a MT targeted PET ligand in prostate, glioblastoma and breast cancer cells. Methods: [11C]MPC-6827 was synthesized by reacting corresponding desmethyl precursors with [11C]CH3I in a GE-FX2MeI/FX2M radiochemistry module. In vitro binding of [11C]MPC-6827 was performed in breast cancer MDA-MB-231, glioblastoma (GBM) patient-derived tumor (GBM-PDX), GBM U251 and prostate cancer 3 (PC3) cell lines at 37 °C in quadruplicate at 5, 15, 30, 60, and 90 minute incubation time. The nonspecific bindings were determined by incubation with unlabeled microtubule targeting agents MPC-6827, HD-800, colchicine, paclitaxel and docetaxel (5.0 mM). Results: [11C]MPC-6827 provided the highest binding in the breast cancer cell, MDA-MB-231, among all the cells studied, with 90% specific binding. [11C]MPC-6827 binds to glioblastoma PDX and U251 cells with ~50% and 40% specific binding, whereas, prostate cancer cell line, PC3 cells showed 40% specific binding. [11C]MPC-6827 also exhibits binding to the taxane and colchicine binding sites of MTs, in MDA-MB-231 cells. Conclusion: These data indicate that [11C]MPC-6827 can be a promising PET radiotracer for preclinical imaging of the brain and peripheral cancers.

New Records of Octocorallia (Order: Pennatulacea) from Indian Waters.

Present paper dealt with three species viz. Virgularia gustaviana, Virgularia mirabilis and Cavernularia pusilla under the order Pennatulacea reported from Andaman and Nicobar Islands are described and illustrated. They are new distributional recorded to Indian waters.

Fouling communities on ship wreck site in the Gulf of Mannar, India.

The Gulf of Mannar is one of the world’s richest marine biospheres and occupies an area of 10,500 sq.km. Twenty one coral reef islands and small patchy reefs are present between Lat. 800 47’N and Long. 780 12’ E to Lat. 900 15’ N and Long. 790 14’ E. from Pamban to Thoothukudi as an arc. These islands possess a very interesting heterogeneous group of fauna and flora. The study was conducted on a twenty year old ship wreck in the Gulf of Mannar, India. During low tides, remnants of the ship are exposed to about 1.5 meters above the water surface. The entire ship wreck is regarded as an artificial reef that harbors corals, fishes and other fauna. Artificial reefs are beneficial in reef conservation and rehabilitation efforts. Successions of artificial reef communities were preliminarily studied using the Line and Belt transect method to assess the composition of benthic organisms like soft corals (25.6 %) and live corals (23.1 %). The abundance of several common reef fishes is also reported.

Seasonal variations of trace metal accumulation on coral reef in Gulf of Mannar, India.

Investication of trace metal occumulation on coral and reef environment (sediment and water) of the Gulf of Mannar biosphere reserve was studied during July 2007 to June 2008. The samples were collected for analyzing from Thoothukudi and Vembar group of Islands, Gulf of Mannar. The concentration of trace metal in the water are in the order of Fe > Pb > Zn > As > Mn > Cd > Cu and in sediment in the order of Fe > Mn > Pb > Zn > Cu >Cd and in coral rubbles in the order of Fe > Mn > Pb > Zn > Cu > Cd. In the waters the iron ranks first and copper ranks last; in the sediment iron ranks first in concentration and cadmium ranks the last. In corals the iron ranks first and cadmium ranks the last in concentration and during the entire study periods. SPSS two tailed Correlation coefficients between the months and the temporal variablilities of heavy metals were assessed using the monthly data for each component in all stations and analysis of variances (f values) for the water, sediment and coral rubbles between the stations and month during the study period. Conclude that the values recorded at Thoothukdi group of islands were little higher than the Vembar group of islands, and it might be due to discharges pumped from the industrial belt of Thoothukudi, domestic sewages from Thoothukudi town, harbour activities and thermal power plant operation along the southern side of the Gulf of Mannar.

Peroxidative changes in experimental diabetes mellitus.

Changes in the levels of lipid peroxides and antioxidant enzymes were studied in male albino rats with experimental diabetes mellitus. Diabetes was induced by single subcutaneous injection of alloxan (19 mg/100 g body weight). The concentration of malondialdehyde (MDA) showed an increase both in the liver (P less than 0.01) and kidney (0 less than 0.05), while in the heart, there was a decrease (P less than 0.01), as compared to control values. A similar pattern of change was observed in the level of hydroperoxides in the liver and heart. The conjugated dienes showed an elevation during diabetes in all tissues (P less than 0.01). Glutathione levels in heart (P less than 0.01) and kidney were found to be decreased (P less than 0.05) while the liver showed an elevation during long-term diabetes (P less than 0.01). Serum ceruloplasmin showed an increase (P less than 0.05) in diabetes. Antioxidant enzymes superoxide dismutase and catalase decreased in all tissues (P less than 0.01) while the activity of glutathione s-transferase increased in heart, but no change in other tissues. The studies thus show that lipid peroxidation is activated in liver and kidney while heart tissues show some resistance towards lipid peroxidation.

Changes in levels of lipid peroxides and activity of superoxide dismutase and catalase in diabetes associated with myocardial infarction.

Studies were carried out on the metabolism of lipid peroxides and antioxidative enzymes during diabetes and diabetes superimposed with myocardial infarction. Diabetes was induced using alloxan and myocardial infarction was induced by isoproterenol. In the case of diabetic animals there was a decrease in the levels of lipid peroxides in the heart while in the case of diabetes associated with myocardial infarction it was slightly elevated. The activity of superoxide dismutase and catalase showed a decrease in both the groups. Glutathione showed a fall in the case of diabetes and diabetes associated with myocardial infarction while taurine in heart and ceruloplasmin in the serum was elevated. Histopathological changes in the heart tissue showed some focal changes in the case of both diabetes and diabetes associated with myocardial infarction, but the degree of necrosis was much less than in the case of myocardial infarction.

Effect of carnitine on malondialdehyde, taurine and glutathione levels in heart of rats subjected to myocardial stress by isoproterenol.

The effect of carnitine on free fatty acid, malondialdehyde, taurine and glutathione levels in myocardium was studied in rats administered isoproterenol to induce a stress in the myocardium resulting in myocardial ischaemia. Carnitine decreased the levels of free fatty acid and malondialdehyde (an index of lipid peroxidation) when compared to control rats given isoproterenol alone. Taurine and glutathione also registered a fall in the carnitine treated animals when compared to rats treated with isoproterenol alone. The results indicate that carnitine by decreasing the levels of these parameters helps the myocardium to survive from the stress induced by isoproterenol.