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Öğe Analyzing of Production Conditions of 89Zr in the Particle Accelerator(2019) Bulduk, Buğra Gökhun; Ünak, Perihan; Kılçar, Ayfer Yurt; Güldü, Özge Kozguş; Tekin, VolkanNowadays 89Zr is outstanding PET radionuclide with its physical half-life (t1/2 ~ 78 hours), useful decay specifications and so that it is suitable for antibody-based immuno-PET. Relatively oscillated positrons' low decay energies supply to take high-resolution. 89Zr-labeled radiopharmaceuticals, especially as 89Zr-labeled antibodies applications are getting increase day by day. in this study, calculations about production of 89Zr were done and used (p,n) reaction of 89Y target system. For this Q-value, Threshold Energy, Minimum Coulomb Barrier Energy of the reaction were calculated then the cross-sections of this reaction were found using Empire3.2/MALTA code. After determining the irradiation calculations, the bombardment performed. the irradiation was performed in Ankara Sarayköy Nuclear Research and Training Center, proton accelerator. the cyclotron is IBA type Cyclone-30. Then separation part was done with Dowex resine system. After separation 89Zr from the irradiated target system, radioactive 89Zr was obtained purely..Öğe Biocompatible Delivery System for Metformin: Characterization, Radiolabeling and in Vitro Studies(Bentham Science Publ Ltd, 2020) Aydin, Burcu; Ucar, Eser; Tekin, Volkan; Ichedef, Cigdem; Teksoz, SerapBackground: in recent years, the uses of nanotechnology in medicine have an increasing potential as an effective nanocarrier system. These systems are improved with the purpose of maximizing therapeutic activity and minimizing undesirable side-effects. Moreover, radiolabeled nanoparticles can be used as agents for diagnosis and therapeutic purposes in clinical applications. They have three main components: the core, the targeting biomolecule, and the radionuclide. Objective: It is aimed to synthesize Metformin (MET) loaded Solid Lipid Nanoparticles (MET-SLN) and radiolabeled with technetium-99m tricarbonyl core. Methods: the structure of synthesized nanoparticles was characterized by Fourier Transform Infrared Spectroscopy (FTIR). the particle size and morphology of nanoparticles were examined by Dynamic Light Scattering (DLS), and Scanning Electron Microscope (SEM). Quality control studies of radiolabeled MET-SLN [Tc-99m(CO)(3)-MET-SLN] were performed by High-Performance Liquid Radiochromatography (HPLRC) and Thin Layer Radiochromatography (TLRC). Results: the radiolabeling yield of [Tc-99m(CO)(3)-MET-SLN] was found to be 88%. in vitro studies have been performed on cancer lines(MCF7, MDA-MD-231 breast, and HEPG2 liver cancer cells) to determine the biological behavior of Tc-99m(CO)3-MET-SLNs. Conclusion: the results showed that higher uptake values were observed on estrogen-positive MCF7 breast cancer cell line according to estrogen negative MDA-MB-231 breast cancer and HEPG2 liver cancer cell lines.Öğe Biodistribution of Whey Protein Labeled with Tc-99m on Experimental Animals(2021) Parlak, Yasemin; Tekin, Volkan; Müftüler, Fazilet Zümrüt Biber; Topal, Gökçen; Gümüşler, Gül; Akınlı, Mert; Avcıbaşı, UğurIn this study, whey protein was radiolabeled with $Tc-^{99m}$ using the SnCl2 reduction method. The paper electrophoresis technique was done in the radiochromatography studies. SF (saline solution) was used as a suitable mobile phase. At the same time, the labeling yield of ${}^{99m}Tc$WHEY was found to be about 95%. Then, lipophilicity and stability studies were carried out, respectively. Finally, imaging and biodistribution studies were completed using Albino Wistar Rats. In vivo studies showed that ${}^{99m}Tc$WHEY was accumulated in the breast, the ovaria and the pancreas. In conclusion, all results showed that ${}^{99m}Tc$WHEY may be helpful in the diagnosis of the breast, the ovaria and the pancreas in the future.Öğe Biological affinity evaluation of Lawsonia inermis origin Lawsone compound and its radioiodinated form via in vitro methods(Springer, 2015) Tekin, Volkan; Muftuler, F. Zumrut Biber; Guldu, Ozge Kozgus; Kilcar, Ayfer Yurt; Medine, E. Ilker; Yavuz, Murat; Unak, Perihan; Timur, SunaWST-1-based cytotoxicity assay of lawsone (LW) was performed on MCF7, Caco2, BJ and Keratinocyte cells and viabilities were found as over 90 % for all cells. Significant wound healing effect of LW was reported on Keratinocyte cells. Antibacterial and antifungal activities of LW were tested on seven microorganisms with three concentrations and 1,000 A mu g/disc of LW showed antibacterial effect on Bacillus subtilis. In vitro cell incorporation of radioiodinated LW (I-131-LW) was evaluated on same cells. Keratinocyte cells uptake were 5 times more. Consequently, I-131-LW was found usable for researches about especially skin diseases in addition to breast and intestinal cancer.Öğe The effect of radiolabeled antibiotics on biofilm and microorganism within biofilm(Springer, 2018) Avcibasi, Ugur; Demiroglu, Hasan; Sakarya, Serhan; Unak, Perihan; Tekin, Volkan; Ates, BuketThe aim of this study was to investigate the I-131 and I-127 labeled linezolid and moxifloxacin effects of minimum inhibitory concentration, and minimum bactericidal concentration on mature biofilm and microorganism within the biofilm. Linezolid and moxifloxacin were labeled with I-131 and I-127 and chromatography studies were carried out with thin layer radiochromatograpy and high-pressure liquid radiochromatography techniques. Specific activities of radiolabeled LZD and MXF was found to be 53.3 +/- 3.1 and 127.3 +/- 1.1 MBq/A mu mol for [I-131]LZD and 7.6 +/- 0.02 and 55.6 +/- 0.8 MBq/A mu mol for [I-131]MXF, respectively. The minimum inhibitory concentration and Time-Kill of Linezolid and moxifloxacin alone and their I-131 and I-127 labeled forms were tested with a standard strain of meticillin-susceptible StaphylocA +/- ccus aureus. MIC values of LNZ and MXF were 2.96 nmol/mL (1 A mu g/ml) and 0.141 nmol/mL (0.062 A mu g/ml). Time Kills of MXF and LZD were found to be 0.06 and 1 mu g, respectively. Antibiotics labeled with beta-emitting radioactive molecule may be a new theranostics strategy for biofilm infections.Öğe Examination of the Association Between 3,4-Divanillyltetrahydrofuran Lignan (Urtica dioica Origin) and Prostate Cancer Cells by I-131 Radiolabeling(Mary Ann Liebert, Inc, 2020) Tekin, Volkan; Guldu, Ozge Kozgus; Medine, Emin Ilker; Muftuler, Fazilet Zumrut BiberBackground: Prostate cancer is the most common type of cancer for men in many countries. One of the various prostate cancer therapy methods is hormone therapy, and explaining the association between androgen hormones and prostate cancer is a critical role for successful prostate cancer treatment. Materials and Methods: in the current study, the behavior of 3,4- divanillyltetrahydrofuran (DTH) was examined against prostate cancer cells, which have androgen sensitivity differences [LNCaP (+), PC3 (-)]. For this aim, DTH was obtained by extraction of Urtica dioica roots. the molecular structure of isolated compound was confirmed as DTH by liquid chromatography-mass spectrometry and nuclear magnetic resonance spectroscopy analyses. To evaluate the association of androgen sensitivity, DTH was radiolabeled with I-131, and cell uptake assay was performed by using I-131-radiolabeled DTH. Also, cytotoxicity (WST-1) assay of DTH was performed against LNCaP and PC3 cells to determinate the toxic effects of DTH on different androgen mechanisms. Results: the results of assays on cells have shown that DTH lignan behaves different like being more toxic to LNCaP cells than PC3 cells, depending on androgen sensitivity. Conclusion: the results may contribute both the research topics of phytolignan prostate cancer and androgen-sensitive prostate cancer.Öğe Green synthesis of silver nanoparticles by using eugenol and evaluation of antimicrobial potential(Wiley, 2019) Tekin, Volkan; Guldu, Ozge Kozgus; Dervis, Emine; Kilcar, Ayfer Yurt; Uygur, Emre; Muftuler, F. Zumrut BiberThe importance of green synthesis was revealed with advantages such as: eliminating the use of expensive chemicals; consume less energy; and generate environmentally benign products. With this aim, silver nanoparticles (AgNPs) were synthesized by using isolated eugenol from clove extract. Its antimicrobial potential was determined on three different microorganisms. Clove was extracted and eugenol was isolated from this extract. Green synthesis was performed and an anti-microbial study was performed. All extraction and isolation analyses were performed by high-performance liquid chromatography (HPLC); identification and confirmation were achieved using liquid chromatography-mass spectrometry (LC-MS); and scanning electron microscopy was used for characterization. Both HPLC and LC-MS analyses showed that eugenol obtained purely synthesized AgNPs and 20-25-nm-sized and homogeneous shaped particles seen in images. The antimicrobial effects of AgNPs at eight concentrations were determinated against Staphylococcus aureus, Escherichia coli and Candida albicans, and maximum inhibition zone diameters were found as 2.6 cm, 2.4 cm and 1.5 cm, respectively. The results of the antimicrobial study showed that eugenol as a biological material brought higher antimicrobial effect to AgNPs in comparison to the other materials found in the literature.Öğe Hyaluronic acid-modified [F-19]FDG-conjugated magnetite nanoparticles: in vitro bioaffinities and HPLC analyses in organs(Springer, 2018) Yasakci, Volkan; Tekin, Volkan; Guldu, Ozge Kozgus; Evren, Vedat; Unak, PerihanIn this study, we designed and synthesized [F-19]FDG-(2-deoxy-2-[fluorine-19]fluoro-d-glucose) conjugated iron oxide magnetic nanoparticles ([F-19]FDG-MNPs) for hybrid imaging and hyperthermia treatment. MNPs were synthesized, silica coated, and fabricated with TEOS (tetraethyl orthosilicate). They were then covered with hyaluronic acid (HA) to enhance their bioavailability. The modified MNPs were conjugated with [F-19]FDG and optically labeled with ICG (indocyanine green). The in vitro bioaffinities were surveyed in MCF7 and PC3 cell lines. In vivo bioaffinies were determined using Sprague-Dawley rats.Öğe In Vitro Determination of Wound. Healing Potential of Axonge(H M P Communications, 2017) Bilgi, Ahmet; Muftuler, Fazilet Zumrut Biber; Akman, Levent; Medine, Emin Ilker; Bilgi, Pinar Tonbaklar; Guldu, Ozge Kozgus; Gokulu, Sevki Goksun; Tekin, Volkan; Terek, Mustafa CosanBackground. Research on treatment alternatives that improve wound healing is an ever-evolving area in medicine, and a wound healing agent that carries minimal pain, discomfort, and scarring for patients with burn wounds, venous and decubitis ulcers, traumatic wounds, and many others is needed. The phases of wound healing include homeostasis, inflammation, migration, proliferation, and maturation. Adeps suillus (axonge) is known as a therapeutic agent for skin diseases and mainly consists of triglycerides. Objective. In the current study, the proliferation effect of axonge was determined on human normal epidermal keratinocyte (HaCaT) cells and human normal foreskin fibroblast cell line (BJ) cells. Materials and Methods. Experimental steps included preparation of HaCaT and BJ cell lines, axonge's stable tetrazolium salt-based proliferation assay, and evaluation of the wound healing effect of axonge on HaCaT and BJ cells. Results. Axonge concentrations of 3.12 mu g/mL, 6.25 mu g/mL, 12.5 mu g/mL, 25 mu g/mL, and 50 mu g/mL showed no cytotoxic effect on both HaCaT and BJ cells for 24, 48, and 72 hours. Considering the wound area of HaCaT cells, after 6 hours the wound healing effect of the axonge group reached almost 70% and then stopped. According to the results of the study on. BJ cells, after 6 hours axonge wound closure was found to be 50% while the control group was only 10%. Conclusion. On the basis of this study, the authors determined that axonge might have potential for use in wound healing.Öğe In Vitro Incorporation of Radioiodinated Eugenol on Adenocarcinoma Cell Lines (Caco2, MCF7, and PC3)(Mary Ann Liebert, Inc, 2017) Dervis, Emine; Kilcar, Ayfer Yurt; Medine, Emin Ilker; Tekin, Volkan; Cetkin, Buse; Uygur, Emre; Muftuler, Fazilet Zumrut BiberRecently, the synthesis of radiolabeled plant origin compounds has been increased due to their high uptake on some cancer cell lines. Eugenol (EUG), a phenolic natural compound in the essential oils of different spices such as Syzygium aromaticum (clove), Pimenta racemosa (bay leaves), and Cinnamomum verum (cinnamon leaf), has been exploited for various medicinal applications. EUG has antiviral, antioxidant, and anti-inflammatory functions and several anticancer properties. The objective of this article is to synthesize radioiodinated (I-131) EUG and investigate its effect on Caco2, MCF7, and PC3 adenocarcinoma cell lines. It is observed that radioiodinated EUG would have potential on therapy and imaging due to its notable uptakes in studied cells.Öğe An in-vivo pilot study into the effects of FDG-mNP in cancer in mice(Public Library Science, 2018) Aras, Omer; Pearce, Gillian; Watkins, Adam J.; Nurili, Fuad; Medine, Emin Ilker; Guldu, Ozge Kozgus; Tekin, Volkan; Wong, Julian; Ma, Xianghong; Ting, Richard; Unak, Perihan; Akin, OguzPurpose Previously, fluorodeoxy glucose conjugated magnetite nanoparticles (FDG-mNPs) injected into cancer cells in conjunction with the application of magnetic hyperthermia have shown promise in new FDG-mNPs applications. The aim of this study was to determine potential toxic or unwanted effects involving both tumour cells and normal tissue in other organs when FDG-mNPs are administered intravenously or intratumourally in mice. Materials and methods FDG-mNPs were synthesized. A group of six prostate-tumour bearing mice were injected with 23.42 mg/ml FDG-mNPs (intravenous injection, n = 3; intratumoural injection into the prostate tumour, n = 3). Mice were euthanized and histological sampling of tissue was conducted for the prostate tumour, as well as for lungs, lymph nodes, liver, kidneys, spleen, and brain, at 1 hour (n = 2) and 7 days (n = 4) post-injection. A second group of two normal (non-cancerous) mice received the same injection intravenously into the tail vein and were euthanised at 3 and 6 months post-injection, respectively, to investigate if FDG-mNPs remained in organs at those time points. Results In prostate-tumour bearing mice, FDG-mNPs concentrated in the prostate tumour, while relatively small amounts were found in the organs of other tissues, particularly the spleen and the liver; FDG-mNP concentrations decreased over time in all tissues. In normal mice, no detrimental effects were found in either mouse at 3 or 6 months. Conclusion Intravenous or intratumoural FDG-mNPs can be safely administered for effective cancer cell destruction. Further research on the clinical utility of FDG-mNPs will be conducted by applying hyperthermia in conjunction with FDG-mNPs in mice.Öğe Kına yaprağından ekstrakte edilen lawsone bileşiğinin radyoişaretlenerek, in vivo ve in vitro yöntemlerle biyoetkinliğinin incelenmesi(Ege Üniversitesi, 2013) Tekin, Volkan; Biber Müftüler, F. ZümrütŞifalı bitkiler tarih boyunca savaşlarda, yaralanmalarda ve hastalıkların tedavisinde potansiyel rol oynamıştır. Bu bitkilerden biri olan kına bitkisi (Lawsonia inermis), ayurvedik tıptan modern tıpa kadar geçen sürede, bir çok hastalık ve rahatsızlığın tedavisinde kullanılmıştır.. Ayrıca 18. yüzyıldan itibaren, bir çok coğrafyada, cilt, saç ve tırnakların boyanması amacıyla da popüler bir yer edinen kına bitkisi, bu boyar maddeleri yapraklarında taşımaktadır. Turuncu renkli ve hidrofilik bir bileşik olan lawsone (LW) bileşiği, bu boyar maddelerden biridir ve kına bitkisinin ana bileşiğidir. LW bileşiğinin antibakteriyel, antifungal, antioksidan ve antikoagulan özellikleri literatürce desteklenmektedir. Gerçekleştirilen bu tez çalışmasında; LW bileşiğinin biyoetkinliğini değerlendirmek amacıyla kına bitkisi yapraklarından elde edilen toz bidistile su ile ekstrakte edilerek, ekstraktan LW bileşiği, Yüksek Basınçlı Sıvı Kromatografisi (HPLC) sistemi ile saflaştırılmıştır. Saf olarak izole edildiği Nükleer Manyetik Rezonans (NMR) yöntemi ve HPLC sistemi ile doğrulanan LW bileşiği, nükleer tıpta, teşhis ve tedavi amacıyla yaygın olarak kullanılan 131I radyonüklidi ile iodojen yöntemi kullanılarak radyoişaretlenmiştir (131I-LW). Radyoişaretleme verimi İnce Tabaka Radyo Kromatografi (TLRC) sistemi ile belirlenen 131I-LW bileşiğinin stabilite ve lipofilite çalışmaları yapılmıştır. In vitro çalışmalar kapsamında Caco-2 (kolon adenokarsinoma epiteli), MCF-7 (meme adenokarsinoma epiteli), BJ (sünnet derisi epiteli) ve keratinosit (deri epiteli) hücreleri ile sitotoksisite, hücre tutulum ve yara modeli çalışmaları, in vivo çalışmalar kapsamında ise erkek ve dişi Balb/C fareler kullanılarak biyodağılım çalışması yapılmıştır. Ayrıca LW bileşiğinin antibakteriyel ve antifungal aktiviteleri, gram(+) ve gram(-) bakteriler ve Candida albicans mantarı üzerinde değerlendirilmiştir. Bu tez çalışması ile, 131I-LW bileşiğinin dişi farelerde meme, rahim ve yumurtalıkta, erkekler farelerde de mide ve prostatta yüksek tutulum göstermesi ve sitotoksik olmaması nedeniyle bu organlara spesifik bir görüntüleme ve tedavi ajanı olarak kullanılabilirliği yanısıra, radyoişaretli bileşiğin BJ ve keratinosit gibi deri hücrelerine olan spesifitesi, LW bileşiğinin ise bu hücrelerdeki yara iyileştirme gücü ve Bacillus subtilis bakterisi üzerindeki antibakteriyel aktivitesi ortaya konarak, kına bitkisi ile gerçekleştirilen çalışmalara farklı bir perspektif kazandırılarak, geliştirilebilecek bitki kökenli ajanlar ya da ürünler için katkı sağlayacağı düşünülmektedir.Öğe Kına yaprağından ekstrakte edilen lawsone bileşiğinin radyoişaretlenerek, in vivo ve in vitro yöntemlerle biyoetkinliğinin incelenmesi(Ege Üniversitesi, 2014) Tekin, Volkan; Biber Müftüler, Fazilet ZümrütLawsonia inermis, Henna, Lawsone, 131I, Biodistrubition, Cell culture, Cytotoxicity, Antibacterial, Antifungal.;Lawsonia inermis, Kına, Lawsone, 131I, Biyodağılım, Hücre kültürü, Sitotoksisite, Antibakteriyel, Antifungal.;Şifalı bitkiler tarih boyunca savaşlarda, yaralanmalarda ve hastalıkların tedavisinde potansiyel rol oynamıştır. Bu bitkilerden biri olan kına bitkisi (Lawsonia inermis), ayurvedik tıptan modern tıpa kadar geçen sürede, bir çok hastalık ve rahatsızlığın tedavisinde kullanılmıştır.. Turuncu renkli ve hidrofilik bir bileşik olan lawsone (LW) kına bitkisinin ana bileşiğidir. LW bileşiğinin antibakteriyel, antifungal, antioksidan ve antikoagulan özellikleri literatürce desteklenmektedir Gerçekleştirilen bu tez çalışmasında; LW bileşiğinin biyoetkinliğini değerlendirmek amacıyla kına bitkisi yapraklarından elde edilen toz bidistile su ile ekstrakte edilerek, ekstraktan LW bileşiği, Yüksek Basınçlı Sıvı Kromatografisi (HPLC) sistemi ile saflaştırılmıştır. Saf olarak izole edildiği Nükleer Manyetik Rezonans (NMR) yöntemi ve HPLC sistemi ile doğrulanan LW bileşiği, nükleer tıpta, teşhis ve tedavi amacıyla yaygın olarak kullanılan 131I radyonüklidi ile iodojen yöntemi kullanılarak radyoişaretlenmiştir (131ILW). Radyoişaretleme verimi İnce Tabaka Radyo Kromatografi (TLRC) sistemi ile belirlenmiştir. In vitro çalışmalar kapsamında Caco-2 (kolon adenokarsinoma epiteli), MCF-7 (meme adenokarsinoma epiteli), BJ (sünnet derisi epiteli) ve keratinosit (deri epiteli) hücreleri ile sitotoksisite ve hücre inkorporasyon çalışmaları, in vivo çalışmalar kapsamında ise erkek ve dişi Balb/C fareler kullanılarak biyodağılım çalışması yapılmıştır. Ayrıca LW bileşiğinin antibakteriyel ve antifungal aktiviteleri, gram(+) ve gram(-) bakteriler ve Candida albicans mantarı üzerinde değerlendirilmiştir. Bu tez çalışması ile, 131I-LW bileşiğinin dişi farelerde meme, rahim ve yumurtalıkta, erkekler farelerde de mide ve prostatta yüksek tutulum göstermesi ve sitotoksik olmaması nedeniyle bu organlara spesifik bir görüntüleme ve tedavi ajanı olarak kullanılabilirliği yanısıra, radyoişaretli bileşiğin keratinosit hücrelerine olan spesifitesi, LW bileşiğinin ise Bacillus subtilis bakterisi üzerindeki antibakteriyel aktivitesi ortaya konarak, kına bitkisi ile gerçekleştirilen çalışmalara farklı bir perspektif kazandırılarak, geliştirilebilecek bitki kökenli ajanlar ya da ürünler için katkı sağlayacağı düşünülmektedir.Öğe A novel anti-angiogenic radio/photo sensitizer for prostate cancer imaging and therapy: Zr-89-Pt@TiO2-SPHINX, synthesis and in vitro evaluation(Elsevier Science Inc, 2021) Tekin, Volkan; Aweda, Tolulope; Guldu, Ozge Kozgus; Muftuler, F. Zumrut Biber; Bartels, Jennifer; Lapi, Suzanne E.; Unak, PerihanProstate cancer is the most common malignancy and leading cause of cancer deaths in men. Thus, the development of novel strategies for performing combined prostate cancer imaging and therapy methods is crucial and could have a significant impact on patient care. This current study aimed to design a multimodality nanoconjugate to be used for both PET and optical imaging and as a therapeutic radio/photo sensitizer and anti-angiogenesis agent. Initial characterization of this novel nanoconjugate was performed via HPLC, FTIR, TEM and DLS analyses. Pt@TiO2-SPHINX was further evaluated using fluorometric and radiochromatographicmethods. Cytotoxicity, cell uptake and internalizationwere also investigated as well as therapy with photodynamic/radio therapy combinations. Both nanoparticles and nanoconjugates were robustly synthesized according to literature methods. Radiochemistry and cell culture assays showed high Zr-89 radiolabeling efficiency with sufficient stability for studies at later time points. Pt@TiO2-SPHINX was shown to target prostate cancer cells (PC3 and LNCaP), and was non-toxic to normal prostate cells (RWPE-1). This finding was supported by the WST-8 assay and AFM images. The uptake of the compound in prostate cancer cells is significantly higher than prostate normal cells and according to ELISA results, Pt@TiO2-SPHINX can increase anti-angiogenic VEGFA(165b). Additionally, Pt@TiO2-SPHINX dramatically decreased the cell viability of prostate cancer cells when photodynamic and radio therapy were performed at the same time. in vitro results are promising for future studies of Pt@TiO2-SPHINX as a PET imaging agent and anti-angiogenic radio sensitizer. (C) 2021 Elsevier Inc. All rights reserved.Öğe A novel radiolabeled graft polymer: Investigation of the radiopharmaceutical potential using Albino Wistar rats(Pergamon-Elsevier Science Ltd, 2019) Avcibasi, Ugur; Ates, Buket; Unak, Perihan; Gumuser, Fikriye Gul; Gulcemal, Suleyman; Ol, Kevser Kusat; Tekin, VolkanFe3O4 magnetic graft-Lys-poly(HEMA) was synthesized, labeled with Tc-99m for the first time and its radiopharmaceutical potential was investigated using animal models in this study. Quality control procedures were carried out using thin layer radiochromatography. the labeling yield of radiolabeled polymer was found to be about 100%. Then, stability and lipophilicity were determined. the lipophilicity of Tc-99m labeled Fe3O4 graft-Lys-poly(HEMA) was found to be 3.77. the serum stability experiments demonstrated that approximately 100% of radiolabeled polymer existed as an intact complex in the rat serum within 240 min. Biodistribution of radiolabeled magnetic graft-Lys-poly(HEMA) was performed on female Albino Wistar rats by scintigraphy and biodistribution studies. High uptake was seen in the stomach, the pancreas, brain, ovarian, intestines and the breast.Öğe A Pilot Study Into the Use of FDG-mNP as an Alternative Approach in Neuroblastoma Cell Hyperthermia(Ieee-Inst Electrical Electronics Engineers Inc, 2016) Subramanian, Mahendran; Pearce, Gillian; Guldu, Ozge Kozgus; Tekin, Volkan; Miaskowski, Arkadiusz; Aras, Omer; Unak, PerihanHerein, we present a pilot study concerning the use of fluorodeoxy glucose conjugated magnetite nanoparticles (FDG-mNP) as a potential agent in magnetic nanoparticle mediated neuroblastoma cancer cell hyperthermia. This approach makes use of the 'Warburg effect', utilizing the fact that cancer cells have a higher metabolic rate than normal cells. FDG-mNP were synthesized, then applied to the SH-SY5Y neuroblastoma cancer cell line and exposed to an ac magnetic field. 3D Calorimetry was performed on the FDG-mNP compound. Simulations were performed using SEMCAD X software using Thelonious, (an anatomically correct male child model) in order to understand more about the end requirements with respect to cancer cell destruction. We investigated FDG-mNP mediated neuroblastoma cytotoxicity in conjunction with ac magnetic field exposure. Results are presented for 3D FDG-mNP SAR mnp (10.86 +/- 0.99 W/g of particles) using a therapeutic dose of 0.83 mg/mL. Human model simulations suggest that 43 W/kg SAR Theo would be required to obtain 42 degrees C within the centre of a liver tumor (Tumor size, bounding box x = 64, y = 61, z = 65 [mm]), and that the temperature distribution is inhomogeneous within the tumor. Our study suggests that this approach could potentially be used to increase the temperature within cells that would result in cancer cell death due to hyperthermia. Further development of this research will also involve using whole tumors removed from living organisms in conjunction with magnetic resonance imaging and positron emission tomography.Öğe PLGA encapsulation and radioiodination of indole-3-carbinol: investigation of anticancerogenic effects against MCF7, Caco2 and PC3 cells by in vitro assays(Springer, 2017) Yildiz, Gorkem; Kilcar, Ayfer Yurt; Medine, E. Ilker; Tekin, Volkan; Guldu, Ozge Kozgus; Muftuler, F. Zumrut BiberEncapsulation 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.Öğe PLGA encapsulation effect on Bioquin-HMPAO: radiolabeling and in vitro behaviour on brain and lung cancer cells(Springer, 2016) Kilcar, Ayfer Yurt; Muftuler, F. Zumrut Biber; Medine, E. Ilker; Tekin, VolkanBioquin-HMPAO (BH) was previously investigated as a novel brain imaging agent by in vivo biodistribution studies. Present studies are carried out to explore radiolabeling and in vitro behaviour evaluation of poly (lactic-co-glycolic acid) (PLGA) encapsulated BH nanocapsules (BH-PLGA NCs). BH-PLGA NCs were characterized utilizing dynamic light scattering and scanning electron microscope. Encapsulation effect on radiolabeling with Tc-99m was examined by stability and lipophilicity studies and effect on in vitro behaviour of Tc-99m-BH was evaluated by incorporation studies on DAOY, U87-MG and A549 cells. It is observed that PLGA encapsulation has a positive and reinforcement effect.Öğe Prostat kanseri hedefli kit tasarımı; platin ve titanyum nanoparçacık temelli konjugatların geliştirilmesi, radyoizotopik modifikasyonlar ve in vitro/in vivo uygulamalar(Ege Üniversitesi, Fen Bilimleri Enstitüsü, 2019) Tekin, Volkan; Ünak, PerihanProstat kanseri erkeklerde sık görülen ve kanser nedeniyle ölümlerinin başında yer alan bir hastalıktır. Risk faktorleri; yaş, etnik köken, aile, genetik ve diğer çevresel faktörler şeklindedir. Prostat kanserinin teşhisinde parmakla rektal muayene, Trans-Rektal ultrason ve Prostat Spesifik Antijen (PSA) testi kullanilmaktadir. Prostat kanserinin tedavisinde ise cerrahi (radikal prostatektomi), eksternal radyoterapi, brakiterapi, yüksek yoğunluklu odaklanmış ultrason (HIFU), kriyoterapi, kemoterapi ve hormon terapi kullanılmaktadır. Bununla birlikte nanobilimin, birçok alanda olduğu gibi özellikle kanser araştırmaları için önemi giderek artmaktadır. Nanoparçacıklar özellikle soymetal olanlar optik ve elektronik etkileri nedeniyle önemli avantajlara sahiptir. Platin nanoparçacıklar intrinsik katalitik özellikleri ve optik özellikleri nedeniyle teşhis ve tedavi için oldukça uygundur. Titanyum nanoparçacıklar ise yüksek stabilite, düşük maliyet ve çevreye karşı güvenilirliği nedeniyle fotokataliz için ideal bir yarı iletken olarak kabul edilmektedir. Özellikle kompozit olarak kullanıldığında, sinerjistik bir etki yaratarak tek başına olduklarından daha güçlü bir etkiye sahip oldukları görülmüştür. Bununla birlikte SPHINX bileşiğinin, yeni kan damarı oluşumunda (anjiyogenez) anjiyojenik faktör olarak anahtar rol oynayan vasküler endotel büyüme faktörü A (VEGF-A) ailesinin VEGFA165a üyesinin üretilmesini sağlayarak anti-anjiyogeneze sebep olduğu görülmüştür. Bu nedenle tez çalışmasında, farklı etkilere sahip bu üç bileşenin konjugasyonu ile multimodal etkilere sahip bir nanokonjugat tasarlanmıştır. Karakterizasyon için Yüksek Performanslı Sıvı Kromatografi (HPLC), Dinamik Işık Saçılımı (DLS), Transmisyon Elektron Mikroskopu (TEM) kullanılarak nanokonjugata ait boyut ve morfoloji tespit edilmiştir. Nanokonjugat 131/125I ile radyoişaretlenerek gama kameralar için, 89Zr ile radyoişaretlenerek ise PET görüntüleme için potansiyele sahip olması hedeflenmiştir. HPLC ve İnce Tabaka Radyokromatografi (TLRC) ile kalite kontrolleri yapılan radyoişaretli örneklerle stabilite ve lipofilite çalışmaları yapılmış ve PC3, LNCaP ve RWPE-1 hücreleri ile hücre çalışmaları gerçekleştirilmiştir. Hücre çalışmaları kapsamında sitotoksisite, hücre tutulum, fotodinamik terapi/radyoterapi simulasyonu ve ELISA gerçekleştirilmiştir. Hücre çalışmaları verileri doğrultusunda, immün sistemi baskılanmış hayvanlar ile PC3 ve LNCaP ksenograft tümör modelleri geliştirilmiş ve 89Zr radyoişaretli nanokonjugat enjekte edilen erkek fareler ile PET çekimleri yapılmıştır. Çalışmalar sonucunda sentezlenen Pt-TiO2-Spx nanokonjugatının PC3 ve LNCaP hücrelerinde canlılık oranını azalttığı gözlemlenmiştir. Nanokonjugatın prostat kanser hücrelerinde toksisite gösterirken sağlıklı hücrelere etki etmemesi, Spx bileşiğinin kanser hücrelerindeki Serin Arginin Protein Kinaz (SRPK) inhibisyonu mekanizması ile açıklanmaktadır. Bu sonuç Atomik Güç Mikroskopu (AFM) görüntüleriyle görsel olarak da desteklenmiştir. Bu SRpK inhibisyonu kanser hücrelerine has bir durum olduğu için, nanokonjugat kanser hücrelerine seçici hale getirilmiştir. Hücre tutulum sonuçları da toksisite sonuçları ile paralel bir şekildedir, 131/125I ve 89Zr ile radyoişaretli nanokonjugat PC3 ve LNCaP hücreleri tarafından yüksek oranda tutulurken, RWPE-1 hücrelerine afinite göstermemektedir. Fotodinamik terapi/radyoterapi simülasyon çalışmaları sonucuna göre; nanokonjugatın prostat kanser hücrelerinde, ışık ile uyarıldığında radyasyon hasarını arttırdığı ve artan hasar sonucu hücre ölümünün de arttığı görülmüştür. Sağlıklı prostat hücresi olan RWPE-1'de ise canlılık oranının prostat kanseri hücrelerine göre yüksek olduğu görülmüştür. Bu durum, in vivo uygulamalarında hedef/hedef olmayan doku oranı açısından oldukça önem teşkil etmektedir. ELISA çalışmaları sonucuna göre nanokonjugat uygulandıktan sonra hücrelerin metabolik atıklarını içeren besiyerindeki VEGF165' in anti-anjiyogenik formu olan VEGF165b oranının arttığı, bu durumun nanokonjugatin konjugasyon sonrası da anti-anjiyogenez özelliğini kaybetmediğini göstermiştir. Hayvan çalışmaları sonucunda, 89Zr- Pt-TiO2-Spx nanokonjugatının LNCaP' a kıyasla PC3 ksenograft tümör modelinde daha çok etki ettiği ve hayati organlarda tutulum görülmediği gözlemlenmiştir. Elde edilen in vitro ve in vivo veriler, tasarlanan Pt-TiO2-Spx nanokonjugatının 131/125I ve 89Zr ile radyoişaretlenerek, prostat kanseri multimodal teşhis ve tedavisi için özellikle hedef/hedef olmayan doku oranı açısından güçlü bir potansiyele sahip olduğunu ortaya koymuştur.Öğe Protoporphyrin-IX and Manganese Oxide Nanoparticles Encapsulated in Niosomes as Theranostic(Wiley-V C H Verlag Gmbh, 2020) Ozada, Cagatay; Tekin, Volkan; Barlas, F. Baris; Timur, Suna; Unak, PerihanPurpose of this study is to develop a multifunctional theranostic agent for both imaging (MR and fluorescence) and combined therapy (photodynamic and radiotherapy). Initially, manganese oxide nanoparticles (MnO NPs) were synthesized and conjugated with diethylenetriaminepentaacetic acid (DTPA) which will be then called as MnO-DTPA NPs, and at the final step, synthesized MnO NPs were encapsulated with niosomes in the presence of protoporphyrin-IX (PP(IX)). in vitro cell culture and bioaffinity studies were performed on PC-3 and BJ cells. the structures (Niosome-MnO-DTPA-PP(IX)) have fluorescence properties and photodynamic therapy potential due to the presence of PP(IX) as well as MR imaging and photodynamic and radiotherapy efficiency. According to data, it was claimed that toxicity of MnO NPs were significantly decreased after encapsulation of niosomes especially for BJ cell line. Therapy potential of the 'Niosome-MnO-DTPA-PP(IX)' was examined and promising findings were obtained for the potential use of combined therapy agent for prostate cancer cells.
