Investigation of in vitro efficiency of magnetic nanoparticle-conjugated I-125-uracil glucuronides in adenocarcinoma cells

WOS: 000295609700029Modification of the magnetic properties of a drug can be used to direct the drug to the desired site, enhancing its therapeutic effectiveness and reducing side effects. In this study, surface-modified magnetic nanoparticles were immobilized with uracil glucuronide derivatives and then labeled with I-125. The morphology, structure, and composition of the magnetic particles were examined by TEM, SEM, VSM, and XRD. The particles sizes were about 50 nm. The labeling yield was 93.8% for uracil-O-glucuronide-immobilized magnetic particles and 95.0% for uracil-N-glucuronide-immobilized magnetic particles. The cell incorporation rates of N- and O-glucuronides were higher than those of uracil. The incorporation rates of uracil-, O-glucuronide-, and N-glucuronide-conjugated magnetic particles were all high. The cell incorporation rates of ligand-conjugated magnetic particles increased under a magnetic field.TUBITAKTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [105 S 486]; Ege UniversityEge University [06 NBE 03, 07 ILAM 01]This work has been financially supported by TUBITAK (contract no 105 S 486), Ege University Research Fund (contact no 06 NBE 03), and Ege University Research Fund (contact no 07 ILAM 01). The authors thank Adnan Menderes University Science Technology Research and Application Centre for conducting the cell culture experiments

Tc-99m labeled plumbagin: estrogen receptor dependent examination against breast cancer cells and comparison with PLGA encapsulated form

WOS: 000372268800003Plant origin products having anticancer properties come into prominence due to widespread of cancer. Plumbagin has various biological activities like anticancer activity. Estrogen receptor (ER) specificity of plumbagin (PL) and radiolabeled PL investigated by in vitro studies on ER+ and ER- adenocarcinoma cells. Additionally, PLGA encapsulation was carried out to reduce toxicity of plumbagin and encapsulation effect was investigated. Plumbagin radiolabeled with 100 % in yields and had ER specificity. Furthermore, PLGA encapsulation effected positively on properties of plumbagin; reduced toxicity, increased stability and ER specificity. A promising agent for the diagnosis of ER+ breast cancer is suggested.Ege UniversityEge University [2014 NBE 004]Current work is supported by Ege University Research Fund (contract no 2014 NBE 004). The authors thank to Busra Karatay and Gorkem Yildiz for the technical assistance during the assays

Somatostatin with Tc-99m and biodistribution studies in rats

WOS: 000252265700004PubMed ID: 18158765Somatostatin (SST) is a short-lived peptide hormone that regulates the endocrine system. The main use of the derivatives of SST is to diagnose diseases related to growth hormone and to use against some forms of cancer that involve growth hormone. Also, SST suppresses gastric acid secretion, gallbladder contractions, and pancreatic enzyme secretion. In this study, two different bifunctional chelating agents were used to examine the changes in the biologic half-life of SST. For this purpose, first D-penicillamine (DPA) and diethylene triaminepentaacetic acid (DTPA) were used to label SST with Tc-99m and then radiopharmaceutical potential of three Tc-99m-labeled complexes, Tc-99m-D-PA, (TC)-T-99m-D-PA-SST, and (99m)TcDTPA-SST, were compared with each other. Quality control for each labeled complex was established by using radiochromatographic methods. The radiolabeled complexes maintained their stabilities for 5 hours. Then, biodistribution studies were performed on Albino Wistar rats independently for three complexes. The results demonstrated that (TC)-T-99m-D-PA-SST exhibited long-term uptake in organs, and its clearance took longer than the Tc-99m-DTPA-SST complex

PHA-L lectin and carbohydrate relationship: conjugation with CdSe/CdS nanoparticles, radiolabeling and in vitro affinities on MCF-7 cells

WOS: 000329299200104This research aims to investigate the interaction between phytohemagglutinin-L (PHA-L) and sialic acid, which is abundant on the breast cancer cell (MCF-7) surface and displays monosaccharide characteristics, by experimental and computational methods. Experimentally, CdSe/CdS nanoparticles (QDs) were synthesized; PHA-L was conjugated with QDs and labeled with I-125. Radiolabeling yield was found to be 97 +/- A 1.2 %. Afterwards, in vitro bioaffinities of radiolabeled PHA-L conjugated QDs have been investigated on MCF-7 cells and it has been observed that the cell incorporation increased with time. The results indicated that I-125 labeled QD-PHA-L conjugates represent significant affinity on MCF-7 cells. In the second step of the study, the crystal structure of carbohydrate interaction surface of PHA-L was extracted from the crystal structure of PHA-L. The interactions between this surface and sialic acid were calculated by computational tools. These calculations revealed specific interactions between PHA-L and sialic acid. Semi-empirical methods, PM3 and AM1, were used in these calculations. Significant outcomes have been obtained from the experimental and computational studies and these results demonstrated that PHA-L may be an effective agent for imagining MCF-7 cells

Synthesis and biodistribution studies of two novel radiolabeled estrone derivatives

WOS: 000253841300016PubMed ID: 18396789Background: Two Tc-99m-DTPA attached estrone derivatives were synthesized and their radiopharmaceutical potential was determined using female albino Wistar rats. Materials and Methods: Two novel radiolabeled estrone derivatives, Tc-99m-2,2',2 '',2'''-(2,2-(2-(3-methoxy-13-methyl-17-oxo- 7, 8, 9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-2-ylamino)-2-oxoethylazanediyl) bis(ethane-2,1-diyl))bis(azanettiyl) tetraacetic acid (Tc-99m-2-DTPA-3-methoxy estrone) and Tc-99m-2,2',2 '',2'''-(2,2'-(2-(3-methoxy-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro- 6H-cyclopenta[a]phenanthren-4-ylamino)-2-oxoethylazanediyl) bis(ethane-2,1-dlyl))bis(azanettiyl)tetraacetic acid (Tc-99m-4DTPA-3-methoxy estrone) were synthesized starting from estrone (3-hydroxy-13-methyl-7,8, 9,11,12,13,15,16-octahydro-6H-cyclopenta[a]phenanthren-17(14H)-one) and DTPA anhydride (2-(bis(2-(2,6-dioxomorpholino)ethyl)amino)acetic acid) as potential estrogen receptor imaging agents. The products were crystallized in ethyl alcohol (95%), purified by high performance liquid chromatography (HPLC) and characterized by nuclear magnetic resonance (NMR) and infrared spectroscopy (IR). The effect of the radiolabeled compounds on the biological behaviour of the molecules was evaluated through biodistribution studies in female albino Wistar rats. The rats were sacrificed at various time intervals, their organs were removed, and the activities of organs were counted using a gamma counter equipped with a Cd(Te) solid state detector. Results and Conclusion: Organ uptake was calculated as activity/gram tissue and time versus activity curves were generated. The tissue distribution studies exhibited a receptor-mediated uptake in the target organs of the rats for each compound. Both Tc-99m-2-DTPA-3-methoxy estrone and (99m)Tc4-DTPA-3-methoxy estrone were stable in vitro and were mainly excreted through the hepatobiliary pathway.. The biological data showed that the Tc-99m-2-DTPA-3-methoxy estrone had higher uptake in the target tissues than the Tc-99m-4-DTPA-3-methoxy estrone. The favourable in vitro/in vivo stability and biodistribution profiles suggest that these radioligands are good candidates for further exploration of their potential clinical applications

Evaluation of the efficacy of 99mTc-labeled ascorbic acid on common cold-cough drugs in rats

Multiple-drug therapy is common in current clinical practice. Because of this, people have been ready to embrace simplistic approaches to cold treatment, such as vitamin C and zinc. Ascorbic acid (vitamin C) is mostly administrated together with cough-cold drugs. The aim of this study was to investigate the effect of cough-cold drugs on the uptake of ascorbic acid using 99mTc-ascorbic acid (99mTc-AA) in male albino Wistar rats. Ascorbic acid was labeled with Tc-99m and the distribution of 99mTc-AA was investigated. The uptake of 99mTc-AA was evaluated when administrated alone (group I), with chlorpheniramine maleate (CPR) (group II), with phenylpropanolamine hydrochloride (PPA) (group III), and with acetaminophen (APAP) (group IV). In some organs (apart from kidneys, intestinal system, and stomach) the uptake of 99mTc-AA was not significantly affected by the administration of 99mTc with CPR or 99mTc with APAP at 120 min. On the other hand, there was significant difference in the uptake of 99mTc-AA between groups I and III. The administration of 99mTc-AA with PPA in rats caused an increase of the uptake of 99mTc-AA at 120 min in the investigated organs compared to the administration of 99mTc-AA alone. The present data show that vitamin C might be more effective for the treatment of common cold when coadministered with PPA compared to with CPR, with APAP, or alone. © 2008 Birkhäuser.Acknowledgements The authors gratefully acknowledge the financial support received from the Ege University Department of Scientific (Project number: 2003 NBE 009). -

Magnetic nanoparticle-conjugated and radioiodinated-DESG: in vitro and in vivo efficiency investigation

WOS: 000347294600008The purpose of this work is to combine magnetite nanoparticles with radioiodinated diethylstilbestrol-glucuronide (DESG) to get a prostate cancer agent. Magnetically targeted drug delivery by particulate carriers is an efficient method of delivering drugs to localized and targeted disease sites, such as tumors. Estrogen glucuronide derivative; DESG was synthesized which is specific for beta glucuronidase enzyme consisting tumor cells and conjugated with iron oxide nanoparticles (NP) and radioiodinated with I-125/131 to evaluate in vitro/in vivo radiopharmaceutical potential of NP conjugated DESG (NP-DESG) and magnetic field applied NP-DESG (MNP-DESG). According to cell culture studies, incorporation ratios of MNP-DESG were higher in MCF7 cells than A549 and Caco2 cells. Biodistribution experiments were verified that the range of the breast/blood and breast/muscle ratios was approximately between 1.82 and 10.10 in 240 min for ER unsaturated studies. The results are promising for targeted therapy of both estrogen receptor and enzyme beta-glucuronidase rich cancers.Ege University Scientific Research FundEge University [2009 NBE001]Authors thank to Ege University Scientific Research Fund with the Project Number 2009 NBE001 for the financial support

Enzymatic synthesis of I-125/131 labeled 8-hydroxyquinoline glucuronide and in vitro/in vivo evaluation of biological influence

WOS: 000287063700003PubMed ID: 211094468-Hydroxyquinoline (8-OHQ) is a long-known molecule which due to its metal-complexation ability is frequently used for analysis. It is also called oxine. Oxine and derivatives have been investigated to process antitumor and antimicrobial activities. 8-Hydroxyquinolyl-glucuronide (8-OHQ-Glu) was enzymatically synthesized using microsome preparates separated from Hutu-80 cells, labeled with I-125 to perform a radionuclide labeled prodrug and investigated of its biological affinities on Hutu-80 (human duodenum intestinal adenocarcinoma), Caco-2 (human colorectal adenocarcinoma), Detroit 562 (human pharynx adenocarcinoma) cells and ACBRI 519 (primary human small intestine epithelial cells) in this work. UDP-glucuronyl transferase (UDPGT) rich microsome preparates, which are used for glucuronidation in enzymatic synthesis, were extracted from Hutu-80 cells. 8-OHQ-Glu components were labeled using iodogen method with I-125 and I-131. Structural analyses were performed with LC/MS/MS, H-1 NMR and C-13-MMR for identify and measure chemical constituents. Results confirmed expected molecular structure. 8-OHQ-Glu could successfully radioiodinated with I-125/131 according to iodogen method. I-125-8-OHQ-glucuronide incorporated with human gastrointestinal cancer cells such as Detroit-562 (human pharynx adenocarcinoma) (12.6%), Caco-2 (human colorectal adenocarcinoma) (7.8%), Hutu-80 (human duodenum intestinal adenocarcinoma) (9.5%) and ACBRI 519 (primary human small intestine epithelial cells) (6.40%). I-131-8-OHQ-Glu was tested in mice bearing subcutaneously implanted Caco-2 colorectal adenocarcinoma cells. The results demonstrated that radioiodinated 8-OHQ-Glu may be promising anticancer prodrug. (C) 2010 Elsevier Ltd. All rights reserved.Aegean UniversityEge University [2008 NBE 05]This work was funded by Aegean University Research Fund (Contact no. 2008 NBE 05)

PLGA encapsulation and radioiodination of indole-3-carbinol: investigation of anticancerogenic effects against MCF7, Caco2 and PC3 cells by in vitro assays

1st International Conference on Radioanalytical and Nuclear Chemistry (RANC) -- APR 10-15, 2016 -- Budapest, HUNGARYWOS: 000394343200012Encapsulation with PLGA of I3C and radioiodination have been performed. Anticancerogenic effects of I3C and I3C-PLGA have been investigated utilizing in vitro methods on breast adenocarcinoma epithelial (MCF7), colon adenocarcinoma epithelial (Caco2), prostate carcinoma epithelial (PC3) cells. Characterization of I3C-PLGA have been performed with DLS method and SEM analysis. I3C and I3C-PLGA compounds have been radiolabeled in high yields with I-131 which is widely used for diagnosis and treatment in Nuclear Medicine. All experimental results demonstrated that radioiodinated compounds are promising in order to be used in Nuclear Medicine as well as present study contributed previously reported studies.Ege University Research FundEge University [2014 NBE 003]Current work is supported by Ege University Research Fund (Contract No 2014 NBE 003). The authors thank to Gokhan Takan for the technical assistance for graphing the particle size distribution of I3C-PLGA according to frequency of particles using GraphPad program (prism 2.01 V)

Gold nanoparticle probes: Design and in vitro applications in cancer cell culture

WOS: 000298518600033PubMed ID: 22070896A new architecture has been designed by the conjugation of [(18)F]2-fluoro-2-deoxy-D-glucose ((18)F-FDG), gold nanoparticles (AuNPs), and anti-metadherin (Anti-MTDH) antibody which is specific to the metadherin (MTDH) over-expressed on the surface of breast cancer cells. Mannose triflate molecule is used as a precursor for synthesis of (18)F-FDG by nucleophilic fluorination. For the conjugation of (18)F-FDG and AuNPs, cysteamine was first bound to mannose triflate (Man-CA) before synthesizing of (18)F-FDG which has cysteamine sides ((18)FDG-CA). Then, (18)FDG-CA was reacted with HAuCl(4) to obtain AuNPs and with NaBH(4) for reduction of AuNPs. At the end of this procedure. AuNPs were conjugated to (18)F-FDG via disulphide bonds ((18)FDG-AuNP). For the conjugation of Anti-MTDH, 1,1'-carbonyl diimidazol (CDI) was bound to the (18)FDG-AuNP, and Anti-MTDH was conjugated via CDI ((18)FDG-AuNP-Anti-MTDH). This procedure was also performed by using Na(19)F to obtain non-radioactive conjugates ((19)FDG-AuNP-Anti-MTDH). Scanning electron microscopy (SEM) images demonstrated that synthesized particles were in nano sizes. (18)FDG-AuNP-Anti-MTDH conjugate was characterized and used as a model probe containing both radioactive and optical labels together as well as the biological target. The (18)FDG-AuNP-Anti-MTDH conjugate was applied to MCF7 breast cancer cell line and apoptotic cell ratio was found to be increasing from 2% to 20% following the treatment. Hence, these results have promised an important application potential of this conjugate in cancer research. (C) 2011 Elsevier B.V. All rights reserved.Ege UniversityEge University [2009 FEN 007]This work was supported by Ege University Research Fund (Project No. 2009 FEN 007). Prof. K.-H. Feller from Jena University is acknowledged for the mass analyses. Prof. Y. Karasulu from Ege University is also acknowledged for her valuable helps during the zeta potential measurements