MCBÜ Açıkerişim Sistemi :: Browsing by Author "Gümüser, FG"

Browsing by Author "Gümüser, FG"

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Radiolabeling fingolimod with technetium-99 m and evaluating its biological affinity by in vitro method
Uygur, E; Parlak, Y; Karatay, KB; Sezgin, C; Gümüser, FG; Müftüler, FZB
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 [Tc-99m]Tc and the biological affinity of [Tc-99m]Tc-FTY-720 was assessed using in vitro methods. The radiochemical yield and stability of [Tc-99m]Tc-FTY-720 was over 95% during 4 h. [Tc-99m]Tc-FTY-720 showed uptake on the SH-SY5Y cell line.
Investigation of the Radiolabelling Potential of the Aurora A Kinase Inhibitor Alisertib with Iodine-123 [123I]
Uygur, E; Sezgin, C; Akdag, BY; Özbey, T; Parlak, Y; Karatay, KB; Gümüser, FG; Müftüler, FZB
Synthesis, radiolabeling and in vivo biodistribution of diethylstilbestrol phosphate derivative (DES-P)
Ünak, P; Müftüler, FZB; Içhedef, Ç; Medine, EI; Özmen, K; Ünak, T; Kilçar, AY; Gümüser, FG; Parlak, Y; Bilgin, ES
Diethylstilbestrol (DES) is a well known, nonsteroidal estrogen with high affinity for the estrogen receptor (ER). Today DES is used to treat breast and prostate cancers. A phosphate derivative of DES [Diethylstilbestrol diphosphate (DES-P)] which is specific to tumor cells consisting alkaline phosphatase enzyme was synthesized and labeled with Tc-99m using tin chloride as reducing agent. In vivo biological activity of Tc-99m labeled diethylstilbestrol phosphate compound (Tc-99m-DES-P) was examined by biodistribution studies on Wistar Albino rats. Statistical evaluation was performed using SPSS 13 program. The percentage (%) radiolabeling yield of Tc-99m-DES-P and quality control studies were done by Thin Layer Radio Chromatography (TLRC). Results showed that, Tc-99m-DES-P may be proposed as an imaging agent for ER enriched tumors such as uterus and prostate and their metastases in bones.
Radiosynthesis and biodistribution of 99mTc-Sulfamethoxazole: a novel molecule for in-vivo infection imaging
Uyaroglu, Ö; Demiroglu, H; Topal, G; Parlak, Y; Gümüser, FG; Türköz, EU; Demir, V; Ates, B; Ünak, P; Avcibasi, U
The aim of this study was to prepare Tc-99m-Sulfamethoxazole complex and evaluate its efficiency as an infection imaging agent. The Sulfamethoxazole was labeled with Tc-99m and its biological efficacy as a potential radio tracer for Staphylococcus aureus infection was investigated in bacterially infected Albino Wistar rats. The radiolabeling yield was found to be 95 +/- 3.07% and remained constant at more than 93 +/- 0.1% even in serum for 240 min after radiolabeling. Tc-99m-Sulfamethoxazole prepared with high yield localized well in the bacterially infected muscle of the rats. Tc-99m-Sulfamethoxazole may be developed as a radiopharmaceutical agent to distinguish infection from inflammation by nuclear imaging.
Metabolic Comparison of Radiolabeled Bleomycin and Bleomycin-Glucuronide Labeled with 99mTc
Koçan, F; Avcibasi, U; Ünak, P; Müftüler, FZB; Içhedef, ÇA; Demiroglu, H; Gümüser, FG
The metabolic comparison of bleomycin (BLM) and bleomycin-glucuronide (BLMG) radiolabeled with Tc-99m (Tc-99m-BLM and Tc-99m-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 Tc-99m, 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 Tc-99m-BLM and Tc-99m-BLMG metabolized as N-glucuronide were observed within 2 hours in the liver, the bladder, and the spinal cord for Tc-99m-BLM and the lung, the liver, the kidney, the large intestine, and the spinal cord for Tc-99m-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 Tc-99m-BLMG was found to be better than that of Tc-99m-BLM.
Radiosynthesis and Biodistribution of 99mTc-Trimethoprim: A Novel Radiolabeled Antibiotic for Bacterial Infection Imaging Using Experimental Animals
Demiroglu, H; Topal, G; Parlak, Y; Gümüser, FG; Türköz, EU; Tekin, V; Ates, B; Ünak, P; Avcibasi, U
In the present article, we focused on the radiolabeling and evaluation of Tc-99m-TMH complex as a potential candidate for infection imaging in vivo. For this; Trimethoprim (TMH) used to treat bacterial infections was investigated to label with Tc-99m. Labeling was performed using thin (II) chloride as a reducing agent at room temperature for 1 h and radiochemical analysis involved thin layer radiochromatography (TLRC) and high pressure liquid radiochromatograpy (HPLRC) methods. The stability of labeled antibiotic was checked in the presence of rat blood serum at 37 degrees C up to 180 min. The maximum radiolabeling yield was found to be 96 +/- 2% and remained constant at more than 85 +/- 1% even in rat serum for 180 min after radiolabeling. Static image of Tc-99m-TMH in male rats demonstrated that important radiation signals are present in the infected site at first glance in 30 min. After 30 min the uptake of the Tc-99m-TMH as ID/g% in the infected muscle (INM) and normal muscle (NM) of the rats were 7.5 +/- 1.5% and 5.00 +/- 1.2%, respectively. In the INM/NM ratio a desirable behavior was observed as the values for the INM/NM increased up to 10.6. Tc-99m-TMH prepared with high yield is able to localize well in the bacterially infected muscle of the rats. As a result, Tc-99m-TMH may be developed as a radiopharmaceutical agent to distinguish infection from inflammation by nuclear imaging.
In vivo biodistribution of 131I labeled bleomycin (BLM) and isomers (A2 and B2) on experimental animal models
Avcibasi, U; Demiroglu, H; Ünak, P; Müftüler, FZB; Içhedef, ÇA; Gümüser, FG
Bleomycins (BLMs; BLM, A2, and B2) were labeled with I-131 and radiopharmaceutical potentials were investigated using animal models in this study. Quality control procedures were carried out using thin layer radiochromatography (TLRC), high performance liquid chromatography (HPLC), and liquid chromatography (LC/MS/MS). Labeling yields of radiolabeled BLMs were found to be 90, 68, and 71%, respectively. HPLC chromatograms were taken for BLM and cold iodinated BLM (I-127-BLM). Five peaks were detected for BLM and three peaks for I-127-BLM in the HPLC studies. Two peaks belong to isomers of BLM. The isomers of BLM were purified with using HPLC. Biological activity of BLM was determined on male Albino Wistar rats by biodistribution and scintigraphic studies were performed for BLMs by using New Zelland rabbits. The biodistribution results of I-131-BLM showed high uptake in the stomach, the bladder, the prostate, the testicle, and the spinal cord in rats. Scintigraphic results on rabbits agrees with that of biodistributional studies on rats. The scintigraphy of radiolabeled isomers (I-131-A2 and I-131-B2) are similiarly found with that of I-131-BLM.
99mTc(I) carbonyl-radiolabeled lipid based drug carriers for temozolomide delivery and bioevaluation by in vitro and in vivo
Ari, K; Uçar, E; Içhedef, Ç; Kilçar, AY; Medine, EI; Parlak, Y; Bilgin, BES; Aydin, B; Gümüser, FG; 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. zeta 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.
Radiolabeling of Bleomycin-Glucuronide with 131I and Biodistribution Studies Using Xenograft Model of Human Colon Tumor in Balb/C Mice
Demiroglu, H; Avcibasi, U; Ünak, P; Müftüler, FZB; Içhedef, ÇA; Gümüser, FG; 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 I-131 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 I-131-labeled BLMG (I-131-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 I-131-BLM and I-131-BLMG were high in the first 30 minutes postinjection. Tumor-bearing animal studies demonstrated that I-131-BLMG was specially retained in colorectal adenocarcinoma with high tumor uptake. Therefore, I-131-BLMG can be proven to be a promising imaging and therapeutic agent, especially for colon cancer in nuclear medical applications.
Synthesis and biodistribution of novel magnetic-poly(HEMA-APH) nanopolymer radiolabeled with iodine-131 and investigation its fate in vivo for cancer therapy
Avcibasi, U; Avcibasi, N; Akalin, HA; Ediz, M; Demiroglu, H; Gümüser, FG; Özçaliskan, E; Türkcan, C; Uygun, DA; 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 Fe3O4 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, I-131. Thin-layer radiochromatography experiments demonstrated that I-131 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 +/- A 0.02. In vivo results obtained by imaging and biological distribution experiments indicated that mag-poly(HEMA-APH) labeled with I-131 [I-131-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 I-131 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.
Investigation of Therapeutic Efficiency of Bleomycin and Bleomycin-Glucuronide Labeled with 131I on the Cancer Cell Lines
Ediz, M; Avcibasi, U; Ünak, P; Müftüler, FZB; Medine, EI; Kilçar, AY; Demiroglu, H; Gümüser, FG; Sakarya, S
The aim of this study is to determine the incorporations of radiolabeled bleomycin (I-131-BLM) and bleomycin-glucuronide (I-131-BLMGLU) on PC-3 (human prostate carcinoma cell line), Caco-2 (human colon adenocarcinoma cell line), Hutu-80 (Human Duodenum adenocarcinoma cell line), and A549 (Human lung adenocarcinoma epithelial cell line) cancerous cell lines. For this purpose, BLM and BLMGLU enyzmatically synthesized were labeled with I-131, quality control studies were done and the incorporation yields of I-131-BLM and I-131-BLMGLU on these cell lines were measured. Quality-control studies showed that the radiolabeling yields were obtained as 95% and 90% for I-131-BLM and I-131-BLMGLU, respectively. Also, as a result of the cell culture studies, it was found that I-131-BLM and I-131-BLMGLU had higher incorporation on PC-3 cells than that of other cell lines. In addition to this, it was reported that the incorporation yield of I-131-BLMGLU was higher than that I-131-BLM. At the end of the study, cytotoxicities of BLM and BLMGLU on PC-3 cancerous cell line were inspected and fluorescent images of BLM and BLMGLU were taken on PC-3 cells by using fluorescein isothiocyanate. In conclusion, cell culture studies demonstrated that the incorporation values of I-131-BLMGLU on the four cell lines were about five to six times higher than I-131-BLM. Radiolabeled glucuronide derivatives can be used in cancer therapy and tumor imaging, depending on the properties of radioiodine for the beta-glucuronidase-rich tissues because glucuronidation leads to rapid and higher incorporation on adenocarcinoma cells.
Metabolic comparison of radiolabeled aniline- and phenol-phthaleins with 131I
Avcibasi, U; Avcibasi, N; Ünak, T; Ünak, P; Müftüler, FZ; Yidirim, Y; Dincalp, H; Gümüser, FG; Dursun, ER
The metabolic comparison of aniline- and phenol-phthaleins radiolabeled with (131)I ((131)I-APH and (131)I-PPH, respectively) has been investigated in this study. To compare the metabolic behavior of these phthaleins and their glucuronide conjugates radiolabeled with (131)I, scintigraphic and biodistributional techniques were applied using male Albino rabbits. The results obtained have shown that these compounds were successfully radioiodinated with a radioiodination yield of about 100%. Maximum uptakes of (131)I-APH and (131)I-PPH, which were metabolized as N- and O-glucuronides, were observed within 2 h in the bladder and in the small intestine, respectively. In the case of verification of considerably up taking of these compounds also by tumors developed in the small intestine and in the bladder tissues, these results can be expected to be encouraging to test these compounds, which will be radiolabeled with other radioiodines such as (125)I, (121)I and (124)I as imaging and therapeutic agents in nuclear medical applications. (C) 2008 Elsevier Inc. All rights reserved.
A novel radiolabeled graft polymer: Investigation of the radiopharmaceutical potential using Albino Wistar rats
Avcibasi, U; Ates, B; Ünak, P; Gümüser, FG; Gülcemal, S; Ol, KK; Akgöl, S; Tekin, V
Fe3O4 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.
The radiolabeling of [161Tb]Tb-PSMA-617 by a novel radiolabeling method and preclinical evaluation by in vitro/in vivo methods
Uygur, E; Sezgin, C; Parlak, Y; Karatay, KB; Arikbasi, B; Avcibasi, U; Toklu, T; Barutça, S; Harmansah, C; Sözen, TS; Maus, S; Scher, H; Aras, O; Gümüser, FG; Muftuler, FZB
Prostate cancer (PC) is the most prevalent cancer in elderly men, exhibiting a positive correlation with age. As resistance to treatment has developed, particularly in the progressive stage of the disease and in the presence of microfocal multiple bone metastases, new generation radionuclide therapies have emerged. Recently introduced for treating micrometastatic foci, Terbium-161 ([Tb-161]) has shown great promise in prostate cancer treatment. This study investigated the in vitro and in vivo cytotoxicity of Terbium-161 ([Tb-161])-radiolabeled prostate-specific membrane antigen (PSMA)-617. [Tb-161]Tb-PSMA-617 (7.4 MBq/nmol) demonstrated a radiochemical yield of 97.99 +/- 2.01% and hydrophilicity. [Tb-161]Tb-PSMA-617 was also shown to have good stability, with a radiochemical yield of over 95% up to 72 h. In vitro, [Tb-161]Tb-PSMA-617 exhibited cytotoxicity on LNCaP cells but not on PC3 cells. In vivo, scintigraphy imaging visualized the accumulation of [Tb-161]Tb-PSMA-617 in the prostate, kidneys, and bladder. The results suggest that [Tb-161]Tb-PSMA-617 can be an effective radiolabeled agent for the treatment of PSMA positive foci in prostate cancer.
Preparation of a 99mTc-labeled graft polymer and its in vitro and in vivo evaluation
Avcibasi, U; Türkyarar, T; Karadag, A; Bakan, B; Yavasoglu, NÜK; Kusat, K; Akgöl, S; Gülcemal, D; Tekin, V; Müftüler, FZB; Topal, G; Parlak, Y; Gümüser, FG
The aim of this study is the synthesis of a novel Tc-99m-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 Tc-99m. The radiochemical yield of approximately the Tc-99m-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.
Synthesis, radiolabeling and in vitro evaluation of azathioprine loaded magnetic solid lipid nanoparticles
Türkkani, G; Güngör, B; Cetin, O; Içhedef, Ç; Parlak, Y; Gümüser, FG; Bilgin, BES; Teksöz, S
In this study, it is aimed to design a smart drug delivery system for the diagnosis and treatment of cancer cells. Magnetic-solid lipid nanoparticles were synthesized as a drug delivery system and azathioprine (AZA) was loaded into this system. This newly created system was radiolabeled using technetium-99 m with a radiolabeling yield of 90.3%. Drug loading into the SLMNP was found as 86%. The biological behavior of Tc-99m and radiolabeled magnetic solid lipid nanoparticles loaded with azathioprine (Tc-99m-AZA-SLMNP) was investigated in vitro and in vivo.

Browsing by Author "Gümüser, FG"

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