Regional Radiation Medicine Center

Kolkata, India

Regional Radiation Medicine Center

Kolkata, India
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Baishya R.,CSIR - Central Electrochemical Research Institute | Nayak D.K.,CSIR - Central Electrochemical Research Institute | Karmakar S.,Jadavpur University | Chattopadhyay S.,Variable Energy Cyclotron Center | And 4 more authors.
Chemical Biology and Drug Design | Year: 2015

Development of molecular imaging agents to target tumor has become a major trend in nuclear medicine. With the aim to develop new potential 99mTc-radiopharmaceuticals for targeting tumor, we have synthesized 5-nitroimidazolyl amino acids and RGD-coupled 2-nitroimidazoles. Technetium-99m radiolabeling with high radiochemical purity (>90%) was achieved for all the compounds. The radiolabeled complexes exhibited substantial in vitro stability in saline, serum, and histidine solution (10-2 m). Cell binding studies in EAC and B16F10 cell lines also revealed rapid and comparatively high cellular internalization. Among all the compounds studied, the binding of 99mTc(CO)3-5 to B16F10 cells was moderately inhibited by the competitive peptide c[RGDfV], suggesting specificity of the radioligand toward αvβ3 receptor. However, no significant displacement of bound radioligand was observed when the binding of the 99mTc-labeled complexes to above cells was challenged with excess competitive peptide. Fluorescent microscopy study provided direct evidence of intracellular localization of 5(6)-carboxyfluorescein-labeled 2-nitroimidazolyl-RGD-peptide in αvβ3-positive B16F10 mouse melanoma cell line. The ligands caused only 8-13% of hemolysis toward rat erythrocytes at concentrations as high as 100 μm. Imaging and biodistribution studies were performed in Swiss albino mice bearing induced tumor. 99mTc-1 and 99mTc(CO)3-5 demonstrated a very favorable in vivo profile. Selective uptake and retention in tumor with encouraging tumor/muscle and tumor/blood ratio and significant cellular uptake of fluorescence-labeled-2-nitroimidazolyl RGD indicate the great potentiality of the pharmacophore for further evaluation as potential molecular imaging agent in cancer diagnosis. © 2014 John Wiley & Sons A/S.


Gaonkar R.H.,CSIR - Central Electrochemical Research Institute | Ganguly S.,CSIR - Central Electrochemical Research Institute | Baishya R.,CSIR - Central Electrochemical Research Institute | Dewanjee S.,Jadavpur University | And 4 more authors.
Cancer Biotherapy and Radiopharmaceuticals | Year: 2016

In recent years the authors have reported on 99mTc(CO)3-labeled peptides that serve as carriers for biomolecules or radiopharmaceuticals to the tumors. In continuation of that work they report the synthesis of a pentapeptide (Met-Phe-Phe-Gly-His; pep-1), a hexapeptide (Met-Phe-Phe-Asp-Gly-His; pep-2), and a tetrapeptide (Asp-Gly-Arg-His; pep-3) and the attachment of 3-amino-1,2,4-triazole to the β carboxylic function of the aspartic acid unit of pep-2 and pep-3. The pharmacophores were radiolabeled in high yields with [99mTc(CO)3(H2O)3]+ metal aqua ion, characterized for their stability in serum and saline, as well as in His solution, and found to be substantially stable. B16F10 cell line binding studies showed favorable uptake and internalization. In vivo behavior of the radiolabeled triazolyl peptides was assessed in mice bearing induced tumor. The 99mTc(CO)3-triazolyl pep-3 demonstrated rapid urinary clearance and comparatively better tumor uptake. Imaging studies showed visualization of the tumor using 99mTc(CO)3-triazolyl pep-3, but due to high abdominal background, low delineation occurred. Based on the results further experiments will be carried out for targeting tumor with triazolyl peptides. © Copyright 2016, Mary Ann Liebert, Inc. 2016.


Banerjee I.,CSIR - Central Electrochemical Research Institute | De K.,CSIR - Central Electrochemical Research Institute | Mukherjee D.,CSIR - Central Electrochemical Research Institute | Dey G.,Indian Institute of Technology Kharagpur | And 7 more authors.
Acta Biomaterialia | Year: 2016

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 100 nm. 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. © 2016 Acta Materialia Inc.


Nayak D.K.,CSIR - Central Electrochemical Research Institute | Baishya R.,CSIR - Central Electrochemical Research Institute | Halder K.K.,CSIR - Central Electrochemical Research Institute | Sen T.,Jadavpur University | And 4 more authors.
Metallomics | Year: 2012

The aim of this study was to develop 99mTc(CO) 3-labeled fluoroquinolones as novel SPECT radiopharmaceuticals for imaging bacterial infection. Fluoroquinolones, e.g., ofloxacin (OFX), levofloxacin (LVX), lomefloxacin (LMX) and norfloxacin (NFX) were labeled with a fac-[99mTc(CO)3(H2O)3]+ precursor. The radiochemical purity of the radiopharmaceuticals exceeded 97% as determined by thin layer chromatography and HPLC. No further purification was necessary before injection. The Re(CO)3 complex of one of the fluoroquinolones (levofloxacin) was synthesized using [Re(CO)3(H 2O)3]OTf and Re(CO)5Br precursors in separate experiments and characterized by IR, NMR and mass spectroscopic analysis. These studies revealed the formation of a single species in which the piperazinyl nitrogen and the -COOH group attached to the benzoxazine ring system of quinolone were involved in co-ordination to the Re(CO)3 core. The HPLC elution pattern and retention time of the Re(CO)3-LVX complex were comparable to those of the corresponding 99mTc(CO) 3-complex proving their similarity. When incubated in isotonic saline and serum up to 24 h 99mTc(CO)3-labeled fluoroquinolones exhibited good in vitro stability. Biodistribution studies performed at different time points on rats intramuscularly infected with S. aureus as well as on rats with sterile inflammation revealed a higher uptake in the infected area than the turpentine induced inflamed area. The uptake in infected thigh was significant with 99mTc(CO)3-OFX followed by 99mTc(CO)3-LVX. The mean ratios of the uptake in infected/non-infected thighs were 4.75 and 4.27 at 8 h and 24 h, respectively, for 99mTc(CO)3-OFX and 4.42 and 4.18 at 24 h and 8 h, respectively, for 99mTc(CO)3-LVX. The above abscess to muscle ratios were higher than reported for 99mTc-ciprofloxacin and other 99mTc-labeled fluoroquinolones. Scintigraphy studies also showed a significant uptake in the infectious lesions suggesting that 99mTc(CO)3-fluoroquinolones might be useful as diagnostic agents for targeted delivery in bacterial infection. This journal is © The Royal Society of Chemistry 2012.


Behera A.,Indian Institute of Science | Banerjee I.,Indian Institute of Science | De K.,Indian Institute of Science | Munda R.N.,Indian Institute of Science | And 5 more authors.
Amino Acids | Year: 2013

Peptides are attracting increasing interest in nuclear oncology for targeted tumor diagnosis and therapy. We therefore synthesized new cyclic octapeptides conjugated with HYNIC by Fmoc solid-phase peptide synthesis. These were purified and analyzed by RP-HPLC, MALDI mass, 1H NMR, 13C NMR, HSQC, HMBC, COSY and IR spectroscopy. Conformational analysis of the peptides was performed by circular dichroism spectroscopy, in pure water and trifluoroethanol-water (1:1), revealed the presence of strong secondary structural features like β-sheet and random coils. Labeling was performed with 99mTc using Tricine and EDDA as coligands by SnCl 2 method to get products with excellent radiochemical purity >99.5 %. Metabolic stability analysis did not show any evidence of breaking of the labeled compounds and formation of free 99mTc. Internalization studies were done and IC50 values were determined in somatostatin receptor-expressing C6 glioma cell line and rat brain cortex membrane, and the results compared with HYNIC-TOC as standard. The IC50 values of 99mTc-HYNIC-His3-Octreotate (21 ± 0.93 nM) and 99mTc-HYNIC-TOC (2.87 ± 0.41 nM) proved to be comparable. Biodistribution and image study on normal rat under gamma camera showed very high uptake in kidney and urine, indicating kidney as primary organ for metabolism and route of excretion. Biodistribution and image study on rats bearing C6 glioma tumor found high uptake in tumor (1.27 ± 0.15) and pancreas (1.71 ± 0.03). Using these findings, new derivatives can be prepared to develop 99mTc radiopharmaceuticals for imaging somatostatin receptor-positive tumors. © 2012 Springer-Verlag Wien.


PubMed | CSIR - Central Electrochemical Research Institute, Indian Institute of Technology Kharagpur, Regional Radiation Medicine Center, Variable Energy Cyclotron Center and 2 more.
Type: | Journal: Acta biomaterialia | Year: 2016

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.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.


Halder K.K.,CSIR - Central Electrochemical Research Institute | Nayak D.K.,CSIR - Central Electrochemical Research Institute | Baishya R.,CSIR - Central Electrochemical Research Institute | Sarkar B.R.,Regional Radiation Medicine Center | And 3 more authors.
Metallomics | Year: 2011

The aim of this study was to radiolabel ciprofloxacin (Cip) and nitrofuryl thiosemicarbazone (NFT) with the fac-[ 99mTc(CO) 3(H 2O) 3] + core and to evaluate the ability of the radiopharmaceuticals as tracers in detecting sites of infection. Cip and NFT were radiolabeled with the fac-[ 99mTc(CO) 3(H 2O) 3] + core and characterized by RHPLC. The stabilities of the preparations were evaluated in saline and rat serum. In vitro binding studies of the radiopharmaceuticals with S. aureus were performed. Biodistribution studies were conducted at different time points after injecting (i.v.) the radiopharmaceuticals in rats (intramuscularly infected with S. aureus) as well as in rats with sterile inflammation. To assess the infection targeting capacity of 99mTc-tricarbonyl ciprofloxacin and nitrofuryl thiosemicarbazone, 99mTc(v)O-Cip and 99mTc(v)O-NFT were used as control. Scintigraphic imaging studies of tricarbonyl compounds and 99mTc(v)O-Cip were performed at 4 h after injection. The radiochemical purities of 99mTc(CO) 3-Cip and 99mTc(CO) 3-NFT were between 97-98% as determined by thin layer chromatography (TLRC) and RHPLC; no further purification is necessary before injection. The radiopharmaceuticals exhibited substantial stability when incubated in isotonic saline and serum up to 24 h. Biodistribution studies showed maximum uptake in the infected rat thigh muscle at 4 h post injection and washing out at slower rate from the infected site than the oxo technetium chelate. The mean ratios of uptake in infected/non-infected thighs were 3.87:1, 3.41:1 and 3.17:1 for 99mTc(CO) 3-Cip, 99mTc(CO) 3-NFT and 99mTc(v)O-Cip respectively. During scintigraphic studies, infection sites appeared quite distinctly with 99mTc(CO) 3-Cip and 99mTc(CO) 3-NFT, comparable to the behaviour with 99mTc(v)O-Cip. These results encouraged us for further development of infection imaging radiopharmaceuticals based on the 99mTc-tricarbonyl core. © 2011 The Royal Society of Chemistry.


De K.,Indian Institute of Science | Chandra S.,Indian Institute of Science | Sarkar B.,Regional Radiation Medicine Center | Ganguly S.,Regional Radiation Medicine Center | Misra M.,Indian Institute of Science
Journal of Radioanalytical and Nuclear Chemistry | Year: 2010

In the recent years interests on dihydropyrimidinone and their analogues have increased potentially due to their wide range of pharmacological/biological activities. Synthesis, radiolabeling with technetium-99 m (99mTc) and biological evaluation of 5-etoxycarbonyl-4-phenyl-6-methyl-3,4-dihydro-(1H)- pyrimidine-2-one (DHPM) were studied in this present work. After synthesis complexation of DHPM with 99mTc was carried out using stannous chloride as the reducing agent. The complex (99mTc-DHPM) was characterized by thin layer chromatography, radio-HPLC technique and determination of partition co-efficient. Radiochemical stability and particle size distribution of the complex were also measured. Biodistribution/ scintigraphy studies were performed in rats and rabbits to evaluate the pharmacological characteristics of this complex. The radiochemical purity of the complex was over 95% as studied by thin layer chromatography and radio-HPLC. It was stable over 24 h at room temperature. Its partition coefficient indicated that it was a lipophilic complex. According to the European Pharmacopeia, >80% of 99mTc labeled radiopharmaceutical (99mTc-MAA) in the size range 10-50 μm, must be accumulated in the lungs 15 min after intravenous administration. In this study >85% of the 99mTc-DHPM complex in the average size of 40 μm. Biodistribution studies of 99mTc-DHPM in rat revealed that the complex accumulated in the lung with high uptake and good retention after intravenous administration. Scintigraphic studies in rabbit also revealed that most of the administered radiolabeled complex was accumulated in the lungs and after 1 h slowly excreted through the renal system. The lung uptake (ID%/g) was 10.12, 9.67, 8.60 and 5.01 and the lung/liver ratio was 7.49, 2.88, 2.62 and 1.87 at 2, 15, 30 and 60 min post-injection, respectively. These results suggested that 99mTc-DHPM could be suitable as a potential lung perfusion imaging agent. Further studies with 99mTc-DHPM and its derivatives are warranted to develop new 99mTc-labeled imaging agents for clinical applications. © 2009 Akadémiai Kiadó, Budapest, Hungary.


Baishya R.,CSIR - Central Electrochemical Research Institute | Nayak D.K.,CSIR - Central Electrochemical Research Institute | Kumar D.,National Institute of Pharmaceutical Education and Research | Sinha S.,Regional Radiation Medicine Center | And 3 more authors.
Pharmaceutical Research | Year: 2016

Purpose: Ursolic acid (UA), a pentacyclic triterpenoid extracted from plants, shows promising inhibitory effect in different tumor bearing cell lines. In the present study we fabricated UA loaded PLGA nanoparticles (UA-NPs) as the drug carrier and thoroughly evaluated in vitro and in vivo the differential tumor targeting effects of UA and UA-NPs in B16F10 melanoma cells. Methods: Ursolic acid loaded PLGA nanoparticles were prepared by emulsion solvent evaporation technique and evaluated for particle size, polydispersity, zeta potential and drug release potency. MTT assay as well as flow cytometric and confocal microscopic analyses were done in B16F10 mouse melanoma cell lines. Formulations were labeled with technetium-99m to evaluate the biodistribution and perform scintigraphic imaging studies following intravenous administration in tumor bearing mice model. Results: Single emulsification technique produced smooth spherical nanoparticles of small size with relatively narrow size distribution (154 ± 4.56 nm). On B16F10 cell line, the formulation showed higher cytotoxicity compared to the free drug due to increased in vitro cellular uptake. The formulation was successfully radiolabeled and remained substantially (>90%) stable when incubated (37°C, 6 h) separately in normal saline or freshly collected rat serum or histidine solution. The radiolabeled UA-NPs exhibited slower blood clearance and comparatively high uptake in tumor region as evidenced by biodistribution and scintigraphic studies. Conclusions: The in vitro and in vivo studies have proved the tumor targeting potential of UA-NPs in B16F10 melanoma cell lines. © 2016 Springer Science+Business Media New York


PubMed | Regional Radiation Medicine Center and CSIR - Central Electrochemical Research Institute
Type: | Journal: Peptides | Year: 2017

Increasing evidence of peptide receptor overexpression in various cancer cells, warrant the development of receptor specific radiolabeled peptides for molecular imaging and therapy in nuclear medicine. Gastrin-releasing-peptide (GRP) receptor, are overexpressed in a variety of human cancer cells. The present study report the synthesis and biological evaluation of new bombesin (BBN) analogs, HYNIC-Asp-[Phe

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