Sankha Chattopadhyay

Synthesis and evaluation of 99mTc-moxifloxacin, a potential infection specific imaging agent

To synthesize and evaluate a (99m)Tc labeled fluroquinolone, moxifloxacin as a potential bacteria specific infection imaging agent. A radiolabeling formulation including moxifloxacin, [Moxicip(TM) injection, Cipla] (4mg), sodium pertechnetate and stannous chloride (5microg) gave the best radiolabeling efficiency and moderately stable labeled (99m)Tc moxifloxacin. Quality control analysis was performed by ITLC. Rats and rabbit with infectious intramuscular lesions induced in either thigh with E. Colli were used for studying biodistribution and scintigraphic imaging of the labeled product. Imaging of an infected thigh of a rabbit was performed with a gamma-camera at various intervals. A good radiolabeling efficiency (90-95%) was obtained within 5min. No purification of the labeled product was done. Labeled product retained its radiochemical purity upto 85% even at 3h. Scintigraphy showed uptake in infectious lesions at 30min after injection, which remains constant upto 3h study. Abscess-to-muscle ratios were 1.60, 1.62, 1.74 and 1.75 at 30min, 1, 2 and 3h, respectively. Thus, (99m)Tc moxifloxacin, a new potential radiopharmaceutical has been developed for infection imaging agent.

Recovery of 99mTc from Na2[99Mo]MoO4 solution obtained from reactor-produced (n,γ) 99Mo using a tiny Dowex-1 column in tandem with a small alumina column☆

A simple separation technique of (99m)Tc from Na(2)[(99)Mo]MoO(4) in sodium hydroxide solution obtained from the (98)Mo(n,gamma)(99)Mo reaction is described. Low to medium specific activity (99)Mo-molybdate solution of 7.4-18.5GBq (200-500mCi) in sodium hydroxide was passed through a tiny Dowex-1 column (25mg) to separate the (99m)Tc from the (99)Mo; subsequently the (99m)Tc was eluted from the Dowex 1 column with tetrabutylammonium bromide (TBAB) solution (1mg/5ml methylene chloride). The TBAB solution was passed through a small alumina column (1.5g) where the (99m)Tc is retained and separated from TBAB and CH(2)Cl(2). Technetium-99m from the alumina column was finally eluted with 5ml saline leaving any traces of (99)Mo on the alumina column. The separation yield was about 90% (n=10). The method has applicability for decontamination of (99g)Tc from spent (99)Mo waste solution and recovery of (99g)Tc for research use. The procedure should also be equally applicable for recovery of (188)ReO(4) from (188)WO(4) in a radioisotope laboratory.

A novel technique for the effective concentration of 99mTc from a large alumina column loaded with low specific-activity (n,γ)-produced 99Mo☆

Molybdenum-99 of low-to-medium specific activity, 7.4-14.8 GBq/g, obtained by the (98)Mo(n,gamma)(99)Mo reaction in research reactors requires a large alumina column to adsorb the molybdenum since the capacity of alumina to adsorb Mo is limited (20 mg Mo/g of alumina). The large size of alumina column, in turn, requires large eluant volumes to elute the (99m)Tc, and the radioactive concentration (RAC) of the pertechnetate becomes unacceptably low for radiopharmaceutical applications. This study describes a method for obtaining high RAC pertechnetate solutions from a column generator loaded with (99)Mo of low specific activity. Molybdenum-99 of specific activity, 7.4 GBq/g, was absorbed on an alumina column [60 g, 70 mm, (H) x 35 mm (diam.)]. The (99m)TcO(4)(-), eluted with 60 ml normal saline (0.15N NaCl), was applied to a 12 mm (H) x 1 mm (diam.) column containing 15 mg of the strong anion exchanger Dowex 1 x 8. The retained pertechnetate was eluted with 5 ml of 0.5 mM tetrabutylammonium bromide (TBAB) solution in methylene chloride. The organic solvent was subsequently removed under vacuum and the dry residue was reconstituted with the desired volume of normal saline. All the operations were carried out in a closed cycle with sterile connecting tubes and multi-way stop-cocks. The concentrated pertechnetate obtained contained about 90% of the total saline eluate and had a pH of 6-7, a radiochemical purity (RCP) consistently >99%, the (99)Mo breakthrough was around 10(-4)%. Colorimetric spot tests (limit tests) for Al and Mo showed <10 ppm in the final (99m)TcO(4)(-) solution. The RCP of the labelled compounds prepared using the pertechnetate obtained and five different radiopharmaceutical kits were >95%. The procedure may be equally applicable for the effective concentration of (188)ReO(4)(-) from (188)W-(188)Re generators.

A simple and rapid technique for recovery of 99mTc from low specific activity (n,γ)99Mo based on solvent extraction and column chromatography

A simple and inexpensive method of separation of (99m)Tc from (99)Mo produced by neutron activation of (98)Mo via the (98)Mo(n,gamma)(99)Mo nuclear reaction is described. The recovery of (99m)Tc was performed by solvent extraction technique followed by column (active alumina) chromatography. The overall radiochemical yield for the complete separation of (99m)Tc was 85-95% (n=10). The separated Na[(99m)Tc]TcO(4) was of high radionuclidic, radiochemical, and chemical purities. The method can be adopted for routine use of (99m)Tc in hospital radio-pharmacies utilizing low-medium specific activity (n,gamma)(99)Mo produced in a research reactor.

Paclitaxel-loaded solid lipid nanoparticles modified with Tyr-3-octreotide for enhanced anti-angiogenic and anti-glioma therapy

UNLABELLED Somatostatin receptors (SSTRs) especially subtype 2 (SSTR2) are overexpressed in glioma. By taking advantage of the specific expression of SSTR2 on both glioma neovasculature endothelial cells and glioma cells, we constructed Tyr-3-octreotide (TOC)-modified solid lipid nanoparticles (SLN) loaded with paclitaxel (PTX) to enable tumor neovasculature and tumor cells dual-targeting chemotherapy. In this work, a TOC-polyethylene glycol-lipid (TOC-PEG-lipid) was successfully synthesized and used as a targeting molecule to enhance anticancer efficacy of PTX loaded sterically stabilized lipid nanoparticles. The prepared PTX-loaded SLN modified with TOC (PSM) was characterized by standard methods. In rat C6 glioma cells, PSM improved PTX induced apoptosis. Both tube formation assay and CD31 staining of treated orthotopic glioma tissues confirmed that PSM significantly improved the antiangiogenic ability of PTX in vitro and in vivo, respectively. Radiolabelled PSM achieved a much higher and specific accumulation within the glioma as suggested by the biodistribution and imaging studies. Furthermore, PSM exhibited improved anti-glioma efficacy over unmodified nanoparticles and Taxol in both subcutaneous and orthotopic tumor models. These findings collectively indicate that PSM holds great potential in improving the efficacy of anti-glioma therapy. STATEMENT OF SIGNIFICANCE Somatostatin receptors (SSTRs) especially subtype 2 (SSTR2) are overexpressed in various mammalian cancer cells. Proliferating endothelial cells of neovasculature also express SSTR2. Tyr-3-octreotide (TOC) is a known ligand for SSTR2. We have successfully prepared paclitaxel-loaded solid lipid nanoparticles modified with TOC (PSM) having diameter less than 100nm. We found that PSM improved anti-cancer efficacy of paclitaxel in SSTR2 positive glioma of rats. This improved anti-glioma efficiency of PSM can be attributed to dual-targeting (i.e. tumor cell and neovasculature targeting) efficiency of PSM and promoted anti-cancer drug accumulation at tumor site due to TOC modification of solid lipid nanoparticles. This particular study aims at widening the scope of octreotide-derivative modified nanocarrier by exploring dual-targeting potential of PSM.

A computerized compact module for separation of 99mTc-radionuclide from molybdenum

An automated closed cycle module for the separation and recovery of various isotopes, radioactive or non-radioactive, using solvent extraction and column chromatography techniques, and in particular, for separation and recovery of (99m)Tc from low-medium specific activity (99)Mo, is described. The module may also be applicable for separation of (99m)Tc produced in a cyclotron. The module is safe and reliable to avoid human interference and hazards posed by handling of radioactive and hazardous chemicals. The entire system of automation includes a user-friendly PC based graphical user interface (GUI) that actually supervises the process via an embedded system based electronic controller.

Preparation and evaluation of 99mTc-cefuroxime, a potential infection specific imaging agent: a reliable thin layer chromatographic system to delineate impurities from the 99mTc-antibiotic.

Technetium-99m labelled cefuroxime, a second-generation cephalosporin antibiotic and potential bacteria specific infection imaging agent was evaluated. A good radiochemical purity (95%) of the labelled product was obtained after filtering the reaction mixture through a 0.22 μm filter. Scintigraphy study of the purified product showed uptake in infectious lesions 45 min after injection and abscess-to-muscle ratios were found to be 1.80, 1.85 and 1.88 at 45 min, 1.5 hr and 3 hr, respectively. A versatile and reliable chromatographic technique to assess the radiochemical purity of (99m)Tc-cefuroxime has also been described.

Recovery of 131I from alkaline solution of n-irradiated tellurium target using a tiny Dowex-1 column

A simple and inexpensive ion-exchange chromatography method for the separation of medically useful no-carrier-added (nca) iodine radionuclides from bulk amounts of irradiated tellurium dioxide (TeO(2)) target was developed and tested using (131)I. The radiochemical separation was performed using a very small Dowex-1x8 ion-exchange column. The overall radiochemical yield for the complete separation of (131)I was 92+/-1.8 (standard deviation) % (n=8). The separated nca (131)I was of high, approximately 99%, radionuclidic and radiochemical purity and did not contain detectable amounts of the target material. This method may be adopted for the radiochemical separation of other different iodine radionuclides produced from tellurium matrices through cyclotron as well as reactor irradiation.

A simple and rapid technique for radiochemical separation of iodine radionuclides from irradiated tellurium using an activated charcoal column.

A simple and inexpensive method for the separation of medically useful no-carrier-added (nca) iodine radionuclides from bulk amounts of irradiated tellurium dioxide (TeO(2)) target was developed. The beta(-) emitting (131)I radionuclide, produced by the decay of (131)Te through the (nat)Te(n, gamma)(131)Te nuclear reaction, was used for standardization of the radiochemical separation procedure. The radiochemical separation was performed by precipitation followed by column (activated charcoal) chromatography. Quantitative post-irradiation recovery of the TeO(2) target material (98-99%), in a form suitable for reuse in future irradiations, was achieved. The overall radiochemical yield for the complete separation of (131)I was 75-85% (n=8). The separated nca (131)I was of high, approximately 99%, radionuclidic and radiochemical purities and did not contain detectable amounts of the target material. This method can be adopted for the radiochemical separation of other different iodine radionuclides produced from tellurium matrices through cyclotron as well as reactor irradiation.

Polymers derived from Xanthomonas campesteris and Cyamopsis tetragonolobus used as retardant materials for the formulation of sustained release floating matrix tablet of atenolol

The objective of the present study was to develop, optimize, in vitro, and in vivo evaluation of floating matrix tablet of atenolol using polymer blend derived from Xanthomonas campesteris and Cyamopsis tetragonolobus that are characterized by release requirements of sustained-release product and to improve the oral bioavailability of the drug. A 3(2) full factorial design was employed to optimize the tablets, where content of polymer blend (X1) and ratio of xanthan gum-to-guar gum (X2) were considered as independent variables. The effects of independent variables on dependent variables, i.e. floating time, diffusion exponent, and time to release 50% of atenolol were evaluated. The in vivo pharmacokinetic parameters of the optimized formulation were compared with the marketed sustained release formulation of atenolol (Aten(®)). The optimized formulation containing 20% (w/w) of polymer blend and 50:50 ratio of xanthan gum-to-guar gum was able to float more than 12h and showed the desired sustained drug release from the tablets. In vivo retention studies in rabbit stomach showed the gastric residence of tablet up to 6h. The in vivo study of optimized tablets illustrated significant improvement in the oral bioavailability of atenolol in rabbits. It can be concluded that floating matrix tablet of atenolol prepared by using xanthan gum and guar gum has potential for sustained release of the drug as well as improved oral bioavailability through enhanced gastric residence time of formulation in stomach.