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Öğe 99m Tc(I) carbonyl-radiolabeled lipid based drug carriers for temozolomide delivery and bioevaluation by in vitro and in vivo(De Gruyter, 2019) Arl K.; Uçar E.; Içhedef Ç.; Yurt Kllçar A.; Medine E.I.; Parlak Y.; Saylt Bilgin B.E.; Aydln B.; Gümüşer F.G.; Teksöz S.In preclinical research radiolabeled nanoparticles have been attracting interest as a new class of imaging probes. Assuming good stability of solid lipid nanoparticles (SLNs) under physiological conditions, radiolabeled SLNs can be used for imaging and measuring uptake in target tissue. Present study was performed to evaluate biological behavior of temozolomide (TMZ) loaded solid lipid nanoparticles (SLN-TMZ) in vivo and in vitro. Lipid nanoparticles were prepared by emulsification and low-temperature solidification method. ? potential, morphology and particle size of nanoparticles were determined. Biological behavior of 99m Tc(CO) 3 + radiolabeled SLN-TMZ were investigated in vitro on U87/Daoy cell lines and in vivo on female Wistar Albino rats. Obtained results of in vitro incorporation, in vivo biodistribution and gamma imaging studies on radiolabeled SLN-TMZ show that the radiolabeled solid lipid nanoparticles could have potential as a drug delivery system for TMZ. © 2019 Walter de Gruyter GmbH, Berlin/Boston 2019.Öğe 99mTc-D-penicillamine-glucuronide: Synthesis, radiolabeling, in vitro and in vivo evaluation(2011) Teksöz S.; Içhedef Ç.A.; Özyüncü S.; Müftüler F.Z.B.; Ünak P.; Medine I.E.; Ertay T.; Eren M.Ş.The current study was aimed at synthesizing a glucuronide derivative of D-penicillamine (D-PA) to be used for imaging purposes. First of all, D-PA-glucuronide (D-PA-Glu) was synthesized by experimental treatments starting with uridine 5'-diphospho-glucuronosyltransferase enzyme rich microsome preparate. Then, the synthesized compound was labeled with technetium ( 99mTc) by using a reduction method with stannous chloride. Quality controls were performed by using high-performance liquid chromatography and thin-layer radio chromatography (TLRC). Radiolabeling yield of 99mTc-D-PA-Glu was more than 98% according to TLRC results. In vitro evaluations of radiolabeled complexes were investigated on PC-3 human prostate cancer cells. 99mTc-D-PA-Glu exhibited more accumulation on PC-3 cells versus 99mTc-D-PA at 240 minutes. In order to determine its radiopharmaceutical potential, biodistribution studies were carried out in male Albino Wistar rats. The biodistribution results of 99mTc-D-PA-Glu, showed the highest uptake in prostate at 120 minutes postinjection with the main excretion route being through kidneys and bladder. 99mTc-D-PA-Glu and 99mTc-D-PA have exhibited different biodistribution results. © 2011, Mary Ann Liebert, Inc.Öğe Bioevaluation of 99mTc(CO) 3-Guanine in vitro and in vivo(2012) Içhedef C.; Şenocak K.; Ertay T.; Teksöz S.; Medine E.I.; Bekiş R.; Ünak P.The aim of this study is to examine biological behaviour of radiolabeled guanine with [Tc(CO) 3] + core in vitro and in vivo. In vitro biological behavior of 99mTc(CO) 3-Gua was evaluated on Lung (A-549), Breast (MCF-7), Colonic (Caco) carcinoma cell lines and normal human bronchial epithelial (NHBE). 99mTc(CO) 3-Gua compound showed high uptake on A-549 cell line when compared to NHBE cell line. Biodistribution characteristics of 99mTc(CO) 3-Gua was evaluated using New Zeland Rabbits. Scintigraphic results showed that a high level of radioactivity was observed in the lungs and liver shortly after administration of the 99mTc(CO) 3-Gua and excretion takes place via both renal and hepatobiliary route. It was concluded that 99mTc(CO) 3-Gua could be used as a nucleotide radiopharmaceutical for imaging purposes. © 2012 Akadémiai Kiadó, Budapest, Hungary.Öğe Bioevaluation of 99mTc(I) carbonyl-radiolabeled amino acid coated magnetic nanoparticles in vivo(Elsevier Ltd, 2019) Büyükok O.; Uçar E.; İçhedef Ç.; Çetin O.; Teksöz S.In this paper, amino acid coated and radiolabeled magnetic nanoparticles (MNPs) were prepared as a potential diagnostic agent. Magnetic nanoparticles were synthesized and functionalized by L-alanine and L-cysteine amino acids in one step. Besides surface functionalization, amino acid coating also provided favourable particle size. Structural characterization was performed by scanning electron microscopy. We obtained 30–38 nm and 22–30 nm diameter ranges with spherical shape for L-alanine and L-cysteine coated nanoparticles, separately. Then L-alanine and L-cysteine coated MNPs were radiolabeled with 99mTc(I)-tricarbonyl core (99mTc(CO)3-Alanine-MNP, 99mTc(CO)3-Cysteine-MNP) with a labeling yield of 63 ± 3% and 74 ± 2%. Pure radiolabeled magnetic particles were obtained by washing them with saline solution, and the radiochemical purity of 99mTc(CO)3-Alanine-MNP and 99mTc(CO)3-Cysteine-MNP were found as 94.3 ± 0.47% and 97.6 ± 1.06% in each of the final solution, respectively. In addition, both radiolabeled nanoparticles were stabile up to 4 h at 37 °C temperature in vitro conditions. After radiolabeling with 99m-Technetium tricarbonyl core, biological behaviour of nanoparticles was evaluated for each in vivo on male Wistar Albino rats. © 2019 Elsevier B.V.Öğe Complexation behavior of guanine with Th4+, UO2 2+, and Ce3+ at various temperatures(2010) Teksöz S.; Içhedef C.A.; Ünak P.The complexation of guanine with Th4+, UO2 2+, and Ce3+ was investigated using the potentiometric method at a constant ionic strength of I = 0.10 mol•dm-3 (KCl) in aqueous solutions at elevated temperatures. For each metal ion, stability constants were obtained from the pH-metric data using the program HYPERQUAD2006. The formation of monomeric and polymeric species was taken into consideration for each ion at (25, 37, and 45) °C. The thermodynamic parameters for the formation of the guanine complexes were calculated. In conclusion, it is indicated that the values of the stability constants change at various temperatures. © 2010 American Chemical Society.Öğe Effect of rosemary (Rosmarinus officinalis) extract on the biodistribution of 99mTc sulphur colloid and on the radiolabeled blood constituents(Sociedade Brasileira de Farmacognosia, 2013) Uçar E.; Teksöz S.; Içhedef C.; Kilçar A.Y.; Ünak P.With this study we evaluated the effects of the herb rosemary (Rosmarinus officinalis L. Lamiaceae) extract on the labeling of blood constituents with technetium-99m (99mTc) labeled sulphur colloid and on the biodistribution of 99mTc-Sulphur Colloid in Wistar albino rats. For this purpose, two groups of animals (male wistar rats, 130-140 g) were treated (1 mL) with a rosemary extract (750 mg/kg body wt.,n=9) and water (control, n=9) separately by gavage for five days. 99mTc-Sulphur Colloid was administrated by intravenous injection; organs/tissues were withdrawn and weighted. Blood was centrifuged, plasma and blood cells were isolated. The radioactivity was counted to calculate the percentage of activity per gram for each organ/tissue and percentage of activity in blood cells and plasma. A signifi cant increase (p<0.05) in the uptake of 99mTc-Sulphur Colloid in the liver after the treatment with rosemary extract was observed. These results indicate that the substances or metabolites of the rosemary extract would change the biodistribution of 99mTc-Sulphur Colloid.Öğe Evaluation of new 99mTc(CO)3 + radiolabeled glycylglycine In Vivo(Bentham Science Publishers, 2019) Şenışık A.M.; İçhedef Ç.; Kılçar A.Y.; Uçar E.; Arı K.; Parlak Y.; Teksöz S.Background: Peptide-based agents are used in molecular imaging due to their unique properties, such as rapid clearance from the circulation, high affinity and target selectivity. Many of the radiolabeled peptides have been clinically experienced with diagnostic accuracy. The aim of this study was to investigate in vivo biological behavior of [99mTc(CO)3(H2O)3]+ radiolabeled glycylglycine (GlyGly). Methods: Glycylglycine was radiolabeled with a high radiolabeling yield of 94.69±2%, and quality control of the radiolabeling process was performed by thin layer radiochromatography (TLRC) and High-Performance Liquid Radiochromatography (HPLRC). Lipophilicity study for radiolabeled complex (99mTc(CO)3-Gly-Gly) was carried out using solvent extraction. The in vivo evaluation was performed by both biodistribution and SPECT imaging. Results: The high radiolabelling yield of 99mTc(CO)3-GlyGly was obtained and verified by TLRC and HPLRC as well. According to the in vivo results, SPECT images and biodistribution data are in good accordance. The excretion route from the body was both hepatobiliary and renal. Conclusion: This study shows that 99mTc(CO)3-GlyGly has the potential to be used as a peptide-based imaging agent. Further studies, 99mTc(CO)3-GlyGly can be performed on tumor-bearing animals. © 2019 Bentham Science Publishers.Öğe Hydrolytic behavior of Th4+, UO2 2+, and Ce3+ ions at various temperatures(2009) Teksöz S.; Acar C.; Ünak P.The hydrolytic behavior of Th4+, UO2 2+, and Ce3+ was investigated using the potentiometric method at elevated temperatures in KC1 medium. For each metal ion, stability constants were obtained from the pH-metric data using the program HYPERQUAD2006. The formation of [Th(OH)]3+, [Th(OH)2]2+, [Th(OH) 3]+, Th(OH)4, [Th4(OH) 8]8+, and [Th6(OH)15]9+ for the thorium ion, [UO2(OH)]+, [(UO2) 2(OH)2]2+, [(UO2),3- (OH)4]2+, and [(UO2)3(OH) 5]+ for the uranyl ion, and [Ce2(OH)] 5+, [Ce2(OH)2]4+, Ce(OH) 3, and [Ce2(OH)5]+ for the cerium ion was taken into consideration. In addition, the effect of temperature on the stability constants was studied, and thermodynamic parameters were derived and discussed. © 2009 American Chemical Society.Öğe Nanosized Radiopharmaceuticals in Preclinical and Clinical Research; [Klinik Öncesi ve Klinik Araştırmalarda Nano Boyutlu Radyofarmasötikler](Galenos Publishing House, 2023) Teksöz S.Radiopharmaceuticals can be successfully applied in nuclear medicine for the diagnosis and treatment of various diseases, especially cancer. As a result of combining of radiopharmaceuticals with nanotechnology, the design of nanosized therapeutic drug delivery systems in healthcare has been a preferred approach in preclinical and clinical studies for at least twenty years. Nanosized drug formulations play a large role in cancer diagnosis and treatment and have several advantages over other conventional chemotherapeutic drug delivery systems. This review describes the current state or clinical application potential of recently developed radionuclide-containing drug delivery systems in preclinical and clinical research, including the design and modifications of these systems and radiolabeling approaches. ©Telif Hakkı 2023 Türkiye Nükleer Tıp Derneği / Nükleer Tıp Seminerleri, Galenos Yayınevi tarafından yayınlanmıştır.Öğe One-step conjugation of glycylglycine with [18F]FDG and a pilot PET imaging study(Springer Netherlands, 2018) Şenk A.M.; İçhedef Ç.; Kılçar A.Y.; Uçar E.; Arı K.; Göksoy D.; Parlak Y.; Sayıt Bilgin B.E.; Teksöz S.This study describes a single step conjugation of Glycylglycine (GlyGly) which is a small peptide, with [18F]FDG via oxime formation. Amiooxy-functionalization of GlyGly (AO-GlyGly) was accomplished through the reaction of Boc-aminooxy succinimide ester. Conjugation reaction was performed at 100 °C for 30 min in a vial containing AO-GlyGly and [18F]FDG solution. The radiolabeled product ([18F]FDG-GlyGly) was obtained with 98.65 ± 0.35% yield without any purification step which makes this method more attractive for 18F radiolabeling. The present study is concluded with an in vivo pilot animal PET study to assess biodistribution and kinetics of chemoselectively [18F]FDG tagged GlyGly in vivo. © 2018, Akadémiai Kiadó, Budapest, Hungary.Öğe Polymer coated iron nanoparticles: Radiolabeling & in vitro studies(Bentham Science Publishers, 2021) Yilmaz S.; Ichedef C.; Karatay K.B.; Teksöz S.Background: Superparamagnetic iron oxide nanoparticles (SPIONs) have been extensively used for targeted drug delivery systems due to their unique magnetic properties. Objective: In this study, it has been aimed to develop a novel targeted99mTc radiolabeled polymeric drug delivery system for Gemcitabine (GEM). Methods: Gemcitabine, an anticancer agent, was encapsulated into polymer nanoparticles (PLGA) together with iron oxide nanoparticles via double emulsion technique and then labeled with99mTc. SPIONs were synthesized by reduction–coprecipitation method and encapsulated with oleic acid for surface modification. Size distribution and the morphology of the synthesized nanoparticles were characterized by dynamic light scattering (DLS) and scanning electron microscopy (SEM), respectively. The radiolabeling yield of SPION-PLGAGEM nanoparticles was determined via Thin Layer Radio Chromatography (TLRC). Cytotoxicity of GEM loaded SPION-PLGA was investigated on MDA-MB-231 and MCF7 breast cancer cells in vitro. Results: SEM images displayed that the average size of the drug-free nanoparticles was 40 nm and the size of the drug-loaded nanoparticles was 50 nm. The diameter of nanoparticles was determined as 366.6 nm by DLS, while zeta potential was found as 29 mV. SPION was successfully coated with PLGA, which was confirmed by FTIR. GEM encapsulation efficiency of SPION-PLGA was calculated as 4±0.16% by means of HPLC. Radiolabeling yield of SPION-PLGA-GEM nanoparticles was determined as 97.8±1.75% via TLRC. Cytotoxicity of GEM loaded SPION-PLGA was investigated on MDA-MB-231 and MCF7 breast cancer cells. SPION-PLGA-GEM showed high uptake on MCF-7, while the incorporation rate was increased for both cell lines with external magnetic field application. Conclusion:99mTc labeled SPION-PLGA nanoparticles loaded with GEM may overcome some of the obstacles in anti-cancer drug delivery because of their appropriate size, non-toxic, and superparamagnetic characteristics. © 2021 Bentham Science Publishers.Öğe Preparation and bioevaluation of 99mTc-carbonyl complex of guanine(2011) Içhedef C.; Teksöz S.; Şenocak K.; Uçar E.; KIlçar A.Y.The aim of this study is to prepare radiolabeled guanine with 99mTc(CO) 3 + core. For this purpose, guanine has been radiolabeled with 99mTc(CO) 3 + core. Quality control study of radiolabeled guanine molecule with 99mTc(CO) 3 + core was performed by thin layer radio chromatography (TLRC) and high performance liquid radio chromatography (HPLRC). The results showed that the radiolabeling yield was quite high (94 ± 3%). Beside that 99mTc(CO) 3-Gua complex has showed good in vitro stability during the 24 h period. Radiopharmaceutical potential of this complex was evaluated in Wistar Albino Rats. It was concluded that 99mTc(CO) 3-Gua could be used as a nucleotide radiopharmaceutical for in vivo applications. © 2011 Akadémiai Kiadó, Budapest, Hungary.Öğe Preparation and characterization of radiolabeled magnetic nanoparticles as an imaging agent(2012) Içhedef C.; Teksöz S.; Ünak P.; Medine E.I.; Ertay T.; Bekiş R.Magnetic nanoparticles were prepared by a reduction-precipitation method and coated with an amino silane coupling agent. Guanine (Gua) was conjugated to the magnetic nanoparticles (MNPs) using glutaraldehyde as a cross-linker. Common techniques (Fourier transform infrared spectroscopy, scanning electron microscopy, X-ray diffraction, and vibrating electron microscopy) were used to assess the properties of the particles. Structural investigations showed that amino silane-coated MNPs had a particle size of about 40-60 nm in diameter with a spherical morphology. The guanine-conjugated MNPs were radiolabeled with 99mTc(I)-tricarbonyl core ( 99mTc(CO) 3-MNP-Gua) with a labeling yield of 72 ± 4 %. Pure radiolabeled magnetic particles were obtained by washing them with saline solution, and the radiochemical purity of 99mTc(CO) 3-MNP-Gua was 98 ± 2 % in the final solution. The biologic distribution of guanine MNPs was assessed in New Zealand rabbits using a gamma camera. In the in vivo experiment, a high level of radioactivity was observed in the lungs and liver soon after intravenous administration of 99mTc(CO) 3-MNP-Gua. © 2012 Springer Science+Business Media B.V.Öğe Somatostatin with 99mTc and biodistribution studies in rats(2007) Acar C.; Teksöz S.; Ünak P.; Müftüler F.Z.B.; Medine E.I.Somatostatin (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 (D -PA) and diethylene triaminepentaacetic acid (DTPA) were used to label SST with 99mTc and then radiopharmaceutical potential of three 99mTc-labeled complexes, 99mTc-D -PA, 99mTc-D -PA-SST, and 99mTc-DTPA-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 99mTc-D -PA-SST exhibited long-term uptake in organs, and its clearance took longer than the 99mTc-DTPA-SST complex. © Mary Ann Liebert, Inc. 2007.Öğe Synthesis and biological evaluation of bisphosphonate compound labeled with 99m Tc(CO) 3 +(Blackwell Publishing Ltd, 2015) Şenocak K.; Teksöz S.; I?hedef C¸.; U?ar E.In this study, radiolabeling of a bisphosphonate, alendronate (Alendronate sodium), was performed with the help of a bifunctional chelating agent. For that purpose, DTPA-NHS (Diethylenetriaminepentaacetic acid dianhydride-N-hydroxysuccinimide) was synthesized with an esterification between DTPA and NHS. Combining the DTPA-NHS ester with alendronate yields the DTPA-Alendronate compound. The structure of synthesized compound was analyzed by 1 H/ 13 C/ 31 P-NMR and HPLC. After then, the labeling with [ 99m Tc(CO) 3 ] + core of synthesized compound was provided. Performing quality controls of newly synthesized [ 99m Tc(CO) 3 -DTPA-Alendronate] complex with thin layer radiochromatography (TLRC) and high-performance liquid radiochromatography (HPLRC), the labeling yield was found as 99%. It was observed that the compound conserves its stability for 24 h in serum media. Biodistribution of the radiolabeled complex was performed on Wistar Albino rats to determine radiopharmaceutical potential of the [ 99m Tc(CO) 3 -DTPA-Alendronate] complex. It is thought that the data gained from this study will contribute to the development of complexes with bisphosphonate. © 2014 John Wiley & Sons A/S.Öğe Thymidine kinase enzyme selective imaging radiopharmaceutical: 99mTc(CO)3-Ganciclovir(2013) Gedik B.; Teksöz S.; Içhedef Ç.; Kilçar A.Y.; Medine E.I.; Uçar E.The aim of this study is to radiolabel ganciclovir, known as having selective antiviral properties against thymidine kinase, with technetium tricarbonylcore (99mTc(CO)3 + and to investigate the biological behavior of this complex in vitro and in vivo. Commercially provided Ganciclovir (GCV) was radiolabeled with 99mTc(CO)3-. Initially, optimum radiolabeling conditions were determined by analyzing factors such as temperature, pH and time. Quality control of the radiolabeled compound was performed. The radiolabeling yield was found to be 97%. The 99mTc(CO)3 -GCV complex also displayed good in vitro stability during the 24 h period. In vitro cell uptake studies showed that the 99mTc(CO)3-GCV complex is highly uptaken in A-549, PC-3, HeLa cell lines according to the control group 99mTc(I)-tricarbonyl core. The knowledge gained from in vivo and in vitro studies of 99mTc(CO)3-GCV could contribute to the development of a new HSV1-tk gene imaging agent. © by Oldenbourg Wissenschaftsverlag, München.
