Browsing by Subject "lipophilicity"
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Item Metabolic comparison of radiolabeled bleomycin and bleomycin-glucuronide labeled with 99mTc(2011) Koçan F.; Avcíbaşí U.; Ünak P.; Müftüler F.Z.B.; Içhedef Ç.A.; Demiroǧlu H.; Gümüşer F.G.The metabolic comparison of bleomycin (BLM) and bleomycin-glucuronide (BLMG) radiolabeled with 99mTc ( 99mTc-BLM and 99mTc-BLMG, respectively) has been investigated in this study. Quality control procedures were carried out using thin-layer radiochromatography and high-performance liquid chromatography. To compare the metabolic behavior of BLM and its glucuronide conjugate radiolabeled with 99mTc, scintigraphic, and biodistributional techniques were applied using male New Zealand rabbits and Albino Wistar rats. The results obtained have shown that these compounds were successfully radiolabeled with a labeling yield of about 100%. Maximum uptakes of 99mTc-BLM and 99mTc-BLMG metabolized as N-glucuronide were observed within 2 hours in the liver, the bladder, and the spinal cord for 99mTc-BLM and the lung, the liver, the kidney, the large intestine, and the spinal cord for 99mTc-BLMG, respectively. Scintigraphy and biodistributional studies performed on the experimental animals have shown that radiopharmaceutical potentials of these compounds are completely different. At the same time, uptake of the 99mTc-BLMG was found to be better than that of 99mTc-BLM. © 2011, Mary Ann Liebert, Inc.Item Indacaterol in chronic obstructive pulmonary disease: An update for clinicians(2012) Yorgancioglu A.Bronchodilation is the cornerstone of chronic obstructive pulmonary disease (COPD) management and is based on regular treatment with one or more long-acting β2 agonists (LABAs). A novel bronchodilator, indacaterol, satisfies the requirements of an efficacious LABA: it has a relatively longer duration of action compared with existing LABAs and a fast onset of action. This review is a presentation of data on indacaterol with respect to its molecular characteristics as well as comparisons with other long-acting bronchodilators. Data from 12 relevant trials show that once-daily indacaterol provides significant, consistent and clinically important improvements in lung function (forced expiratory volume in 1 second), significant improvements in breathlessness and health status at least as good as or better than tiotropium, salmeterol and formoterol, and reduction in requirement for relief medication compared with tiotropium, salmeterol and formoterol. © 2012, SAGE Publications. All rights reserved.Item Radiolabeling of bleomycin-glucuronide with 131I and biodistribution studies using xenograft model of human colon tumor in Balb/C mice(2012) Demiroǧlu H.; Avcibaşi U.; Ünak P.; Müftüler F.Z.B.; Içhedef Ç.A.; Gümüşer F.G.; Sakarya S.Bleomycin-glucuronide (BLMG) is the glucuronide conjugate of BLM. In the present study, BLMG was primarily enzymatically synthesized by using a microsome preparate separated from rat liver, labeled with 131I by iodogen method with the aim of generating a radionuclide-labeled prodrug, and investigated its bioaffinities with tumor-bearing Balb/C mice. Quality control procedures were carried out using thin-layer radiochromatography and high-performance liquid chromatography. Tumor growing was carried out by following Caco-2 cell inoculation into mice. Radiolabeling yield was found to be about 65%. Results indicated that 131I-labeled BLMG ( 131I-BLMG) was highly stable for 24 hours in human serum. Biodistribution studies were carried out with male Albino Wistar rats and colorectal adenocarcinoma tumor-bearing female Balb/C mice. The biodistribution results in rats showed high uptake in the prostate, the large intestine, and the spinal cord. In addition to this, scintigraphic results agreed with those of biodistributional studies. Xenography studies with tumor-bearing mice demonstrated that tumor uptakes of 131I-BLM and 131I-BLMG were high in the first 30 minutes postinjection. Tumor-bearing animal studies demonstrated that 131I-BLMG was specially retained in colorectal adenocarcinoma with high tumor uptake. Therefore, 131I-BLMG can be proven to be a promising imaging and therapeutic agent, especially for colon cancer in nuclear medical applications. © Copyright 2012, Mary Ann Liebert, Inc. 2012.Item Synthesis and biodistribution of novel magnetic-poly(HEMA-APH) nanopolymer radiolabeled with iodine-131 and investigation its fate in vivo for cancer therapy(Kluwer Academic Publishers, 2013) Avcibaşi U.; Avcibaşi N.; Akalin H.A.; Ediz M.; Demiroǧlu H.; Gümüşer F.G.; Özçalişkan E.; Türkcan C.; Uygun D.A.; Akgöl S.Herein, we investigated the biological uptake, distribution, and radiopharmaceutical potential of a novel molecule based on 2-hydroxyethyl methacrylate (HEMA) and anilinephtalein (APH) in the metabolism of Albino Wistar rats. In order to achieve this, we synthesized APH using organic synthesis methods and copolymerized APH with HEMA using a common polymerization method, surfactant-free emulsion polymerization. In the presence of Fe3O 4 particles, we obtained a new generation magnetic-nano-scale polymer, magnetic-poly(HEMA-APH). This new molecule was chemically identified and approved by several characterization methods using Fourier transform infrared spectroscopy, scanning electron microscope, energy dispersive X-ray spectroscopy, electron spin resonance, atomic force microscope, and Zeta particle-size analysis. To evaluate the biological activity in live metabolism and anti-cancer potential of mag-poly(HEMA-APH), molecule was radioiodinated by a widely used labeling technique, iodogen method, with a gamma diffuser radionuclide, 131I. Thin-layer radiochromatography experiments demonstrated that 131I binded to nanopolymer with the labeling yield of 90 %. Lipophilicity and stability experiments were conducted to determine the condition of cold and labeled mag-poly(HEMA-APH) in rat blood and lipid medium. Results demonstrated that radioiodinated molecule stayed as an intact complex in rat metabolism for 24 h and experimental lipophilicity was determined as 0.12 ± 0.02. In vivo results obtained by imaging and biological distribution experiments indicated that mag-poly(HEMA-APH) labeled with 131I [131I-mag-poly(HEMA-APH)] highly incorporated into tissues of the uterus, the ovarian, the prostate, and the lungs in rat metabolism. Based on these results, it may be evaluated that novel mag-poly(HEMA-APH) molecule labeled with 131I is a compound which has a significant potential for being used as an anti-cancer agent. Certain results can only be obtained whether this molecule is applied to adenocarcinoma cell models and tumor-bearing animals. © 2013 Springer Science+Business Media Dordrecht.Item Radiolabeling of new generation magnetic poly(HEMA-MAPA) nanoparticles with 131I and preliminary investigation of its radiopharmaceutical potential using albino Wistar rats(John Wiley and Sons Ltd, 2013) Avcibaşi U.; Demiroǧlu H.; Ediz M.; Akalin H.A.; Özçalişkan E.; Şenay H.; Türkcan C.; Özcan Y.; Akgöl S.; Avcibaşi N.In this study, N-methacryloyl-l-phenylalanine (MAPA) containing poly(2-hydroxyethylmethacrylate) (HEMA)-based magnetic poly(HEMA-MAPA) nanobeads [mag-poly(HEMA-MAPA)] were radiolabeled with 131I [ 131I-mag-poly(HEMA-MAPA)], and the radiopharmaceutical potential of 131I-mag-poly(HEMA-MAPA) was investigated. Quality control studies were carried out by radiochromatographic method to be sure that 131I binded to mag-poly(HEMA-MAPA) efficiently. In this sense, binding yield of 131I-mag-poly(HEMA-MAPA) was found to be about 95-100%. In addition to this, optimum radiodination conditions for 131I-mag-poly(HEMA- MAPA) were determined by thin-layer radiochromatography studies. In addition to thin-layer radiochromatography studies, lipophilicity (partition coefficient) and stability studies for 131I-mag-poly(HEMA-MAPA) were realized. It was determined that lipophilicities of mag-poly(HEMA-MAPA) and 131I-mag-poly(HEMA-MAPA) were 0.12 ± 0.01 and 1.79 ± 0.76 according to ACD/logP algorithm program, respectively. Stability of the radiolabeled compound was investigated in time intervals given as 0, 30, 60, 180, and 1440 min. It was found that 131I-mag-poly(HEMA-MAPA) existed as a stable complex in rat serum within 60 min. After that, biodistribution and scintigraphy studies were carried out by using albino Wistar rats. It was determined that the most important 131I activity uptake was observed in the breast, the ovary, and the pancreas. Scintigraphy studies well supported biodistribution results. Copyright © 2013 John Wiley & Sons, Ltd.Item Investigation of therapeutic efficiency of phenytoin (PHT) labeled with radioactive 131I in the cancer cell lines(Springer Netherlands, 2016) Uzaras C.; Avcıbaşı U.; Demiroğlu H.; Medine E.İ.; Kılçar A.Y.; Müftüler F.Z.B.; Ünak P.The aim of this study is to determine the incorporations of PHT radiolabeled with 131I (131I-PHT) on U-87 MG, Daoy and A549 cancerous cell lines. For this, cold and radio-labeling studies were carried out. The radio-labeling yield of 131I-PHT was obtained about 95 %. Subsequently, cell culture studies were carried out and radio-labeling yields of 131I, 131I-PHT on U-87 MG, Daoy and A549 cancerous cells were investigated. Cell culture studies demonstrated that the incorporation values of 131I-PHT on the three cell lines decreased with increasing radioactivity. Consequently, 131I-PHT may be a good radiopharmaceutical for targeting radionuclide therapy of Central Nervous System Tumors. © 2015, Akadémiai Kiadó, Budapest, Hungary.Item Multifunctional molecular imaging probes for estrogen receptors: 99mTc labeled diethylstilbestrol (DES) conjugated, cuinp quantum dot nanoparticles (DESCIP)(Springer Netherlands, 2017) Moharrami P.; Unak P.; Guldu O.K.; Medine E.I.; Gumuser G.; Bilgin E.S.; Aras O.A theranostic nanoparticle was synthesized based on diethylstilbestrol conjugated with phosphate, copper, and indium (DESCIP) and labelled with 99mTc which can be used for SPECT imaging of ER-enriched cancers. In vitro biological activity of 99mTc-DESCIP was examined in breast adenocarcinoma cells (MCF-7), prostatic carcinoma cells (PC-3), and pulmonary epithelial cells (A-549). In vivo lymph node imaging was performed in normal and receptor blocked female New Zealand rabbits. Results demonstrated that 99mTc-DESCIP and DESCIP has potential for imaging ER-enriched tumors such as breast and prostate tumors, and their metastases in the lung, as well as improving management for their therapies. © 2017, Akadémiai Kiadó, Budapest, Hungary.Item A novel radiolabeled graft polymer: Investigation of the radiopharmaceutical potential using Albino Wistar rats(Elsevier Ltd, 2019) Avcıbaşı U.; Ateş B.; Ünak P.; Gümüşer F.G.; Gülcemal S.; Ol K.K.; Akgöl S.; Tekin V.Fe3O4 magnetic graft-Lys-poly(HEMA) was synthesized, labeled with 99mTc 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 99mTc 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. © 2019 Elsevier LtdItem 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.; Bilgin E.S.; 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.Item Preparation of a 99mTc-labeled graft polymer and its in vitro and in vivo evaluation(Springer Science and Business Media B.V., 2021) Avcıbaşı U.; Türkyarar T.; Karadağ A.; Bakan B.; Yavaşoğlu N.Ü.K.; Kuşat K.; Akgöl S.; Gülcemal D.; Tekin V.; Müftüler F.Z.B.; Topal G.; Parlak Y.; Gümüşer F.G.The aim of this study is the synthesis of a novel 99mTc-labeld graft polymer and the biological evaluation of its in vitro and in vivo properties. To this end, a L-proline-graft-poly(HEMA) was prepared and labeled with 99mTc. The radiochemical yield of approximately the 99mTc-labeled compound amounted to 97 ± 2.3%. The cytotoxicity test revealed no cytotoxic effect after a 24- and 48-h incubation. The results of the hemolysis test showed that hemolysis was non-toxic with an effect level of less than 2%. Subsequently, the biodistribution in healthy rats was determined. High accumulation of the polymer was observed in the pancreas, thyroid and prostate. © 2021, Akadémiai Kiadó, Budapest, Hungary.Item N-Propargylic β-enaminones in breast cancer cells: Cytotoxicity, apoptosis, and cell cycle analyses(John Wiley and Sons Inc, 2023) Ilhan S.; Atmaca H.; Yilmaz E.S.; Korkmaz E.; Zora M.Breast cancer is one of the most common cancers worldwide and the discovery of new cytotoxic agents is needed. Enaminones are regarded to be a significant structural motif that is found in a variety of pharmacologically active compounds however the number of studies investigating the anticancer activities of N-propargylic β-enaminones (NPEs) is limited. Herein we investigated the potential cytotoxic and apoptotic effects of 23 different NPEs (1-23) on human breast cancer cells. Cytotoxicity was evaluated via MTT assay. Apoptotic cell death and cell cycle distributions were investigated by flow cytometry. CM-H2DCFDA dye was used to evaluate cellular ROS levels. Expression levels of Bcl-2, Bax, p21, and Cyclin D1 were measured by quantitative real-time PCR. ADME properties were calculated using the ADMET 2.0 tool. NPEs 4, 9, 16, and 21 showed selective cytotoxic activity against breast cancer cells with SI values >2. NPEs induced apoptosis and caused significant changes in Bcl-2 and Bax mRNA levels. The cell cycle was arrested at the G0/G1 phase and levels of p21 and Cyclin D1 were upregulated in both breast cancer cells. ROS levels were significantly increased by NPEs, suggesting that the cytotoxic and apoptotic effects of NPEs were mediated by ROS. ADME analysis revealed that NPEs showed favorable distributions in both breast cancer cell lines, meaning good lipophilicity values, low unfractionated values, and high bioavailability. Therefore, these potential anticancer compounds should be further validated by in vivo studies for their appropriate function in human health with a safety profile, and a comprehensive drug interaction study should be performed. © 2023 Wiley Periodicals LLC.Item Investigation of Bioactivity of Estragole Isolated from Basil Plant on Brain Cancer Cell Lines Using Nuclear Method(Bentham Science Publishers, 2023) Avcibasi U.; Dewa M.T.; Karatay K.B.; Kilcar A.Y.; Muftuler F.Z.B.Background: In recent years, there has been a significant increase in studies investigating the potential use of plant-origin products in the treatment and diagnosis of different types of cancer. Methods: In this study, Estragole (EST) was isolated from basil leaves via ethanolic extraction using an 80% ethanol concentration. The isolation process was performed using the High Performance Liquid Chromatography (HPLC) method. The EST isolated from the basil plant was radio-labeled with131I using the iodogen method. Quality control studies of the radiolabeled EST (131I-EST) were carried out by using Thin Layer Radio Chromatography (TLRC). Next, in vitro cell, culture studies were done to investigate the bio-affinity of plant-originated EST labeled with131I on human medulloblastoma (DAOY) and human glioblastoma-astrocytoma (U-87 MG) cell lines. Finally, the cytotoxicity of EST was determined, and cell uptake of131I-EST was investigated on cancer cell lines by incorporation studies. Results: As a result of these studies, it has been shown that131I-EST has a significant uptake on the brain cells. Conclusion: This result is very satisfying, and it has encouraged us to do in vivo studies for the molecule in the future. © 2023 Bentham Science Publishers.Item Radiolabeling fingolimod with technetium-99 m and evaluating its biological affinity by in vitro method(Springer Science and Business Media B.V., 2023) Uygur E.; Parlak Y.; Karatay K.B.; Sezgin C.; Gümüşer F.G.; Biber Müftüler F.Z.Fingolimod (FTY-720) is the first oral medication approved by the food and drug administration (FDA) for the treatment of multiple sclerosis. It acts on the central nervous system by crossing the blood–brain barrier and binding to sphingosine-1-phosphate receptors (S1PRs). FTY-720 protects against neural damage caused by mitochondrial dysfunction and cytotoxicity by modulating S1PR1. In this study, FTY-720 was radiolabeled with technetium-99 m [99mTc]Tc and the biological affinity of [99mTc]Tc-FTY-720 was assessed using in vitro methods. The radiochemical yield and stability of [99mTc]Tc-FTY-720 was over 95% during 4 h. [99mTc]Tc-FTY-720 showed uptake on the SH-SY5Y cell line. © 2023, Akadémiai Kiadó, Budapest, Hungary.