Browsing by Author "Kilçar, AY"

Now showing 1 - 7 of 7
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    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.
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    One-step conjugation of glycylglycine with [18F]FDG and a pilot PET imaging study
    Senisik, AM; Içhedef, Ç; Kilçar, AY; Uçar, E; Ari, K; Göksoy, D; Parlak, Y; Bilgin, BES; Teksöz, S
    This study describes a single step conjugation of Glycylglycine (GlyGly) which is a small peptide, with [F-18]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 A degrees C for 30 min in a vial containing AO-GlyGly and [F-18]FDG solution. The radiolabeled product ([F-18]FDG-GlyGly) was obtained with 98.65 +/- 0.35% yield without any purification step which makes this method more attractive for F-18 radiolabeling. The present study is concluded with an in vivo pilot animal PET study to assess biodistribution and kinetics of chemoselectively [F-18]FDG tagged GlyGly in vivo.
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    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.
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    Evaluation of New 99mTc(CO)3+ Radiolabeled Glycylglycine In Vivo
    Senisik, AM; Içhedef, C; Kilçar, AY; Uçar, E; Ari, K; Parlak, Y; Bilgin, ES; 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 [Tc-99m(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 (iIPLRC). Lipophilicity study for radiolabeled complex (Tc-99m(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 mdiolabelling yield of Tc-99m(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 Tc-99m(CO)(3)-GlyGly has the potential to be used as a peptide-based imaging agent. Further studies, Tc-99m(CO)(3)-GlyGly can be performed on tumor-bearing animals.
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    Investigation of therapeutic efficiency of phenytoin (PHT) labeled with radioactive 131I in the cancer cell lines
    Uzaras, C; Avcibasi, U; Demiroglu, H; Medine, EI; Kilçar, AY; Müftüler, FZB; Ünak, P
    The aim of this study is to determine the incorporations of PHT radiolabeled with I-131 (I-131-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 I-131-PHT was obtained about 95 %. Subsequently, cell culture studies were carried out and radio-labeling yields of I-131, I-131-PHT on U-87 MG, Daoy and A549 cancerous cells were investigated. Cell culture studies demonstrated that the incorporation values of (IPHT)-I-131 on the three cell lines decreased with increasing radioactivity. Consequently, I-131-PHT may be a good radiopharmaceutical for targeting radionuclide therapy of Central Nervous System Tumors.
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    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.
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    Synthesis of Novel Plant-Derived Encapsulated Radiolabeled Compounds for the Diagnosis of Parkinson's Disease and the Evaluation of Biological Effects with In Vitro/In Vivo Methods
    Uygur, E; Karatay, KB; Dervis, E; Evren, V; Kilçar, AY; Güldü, OK; Sezgin, C; Çinleti, BA; Tekin, V; Muftuler, FZB
    Parkinson's disease (PD) is a neurodegenerative disorder that affects millions of individuals globally. It is characterized by the loss of dopaminergic neurons in Substantia Nigra pars compacta (SNc) and striatum. Neuroimaging techniques such as single-photon emission computed tomography (SPECT), positron emission tomography (PET), and magnetic resonance imaging (MRI) help diagnosing PD. In this study, the focus was on developing technetium-99 m ([Tc-99m]Tc) radiolabeled drug delivery systems using plant-derived compounds for the diagnosis of PD. Madecassoside (MA), a plant-derived compound, was conjugated with Levodopa (L-DOPA) to form MA-L-DOPA, which was then encapsulated using Poly Lactic-co-Glycolic Acid (PLGA) to create MA-PLGA and MA-L-DOPA-PLGA nanocapsules. Extensive structural analysis was performed using various methods such as Fourier-transform infrared spectroscopy (FTIR), nuclear magnetic resonance spectroscopy (NMR), liquid chromatography-mass spectrometry (LC-MS), thin layer chromatography (TLC), high performance liquid chromatography (HPLC), dynamic light scattering (DLS), and scanning electron microscopy (SEM) to characterize the synthesized products. Radiochemical yields of radiolabeled compounds were determined using thin layer radio chromatography (TLRC) and high performance liquid radio chromatography (HPLRC) methods. In vitro cell culture studies were conducted on human neuroblastoma (SH-SY5Y) and rat pheochromocytoma (PC-12) cell lines to assess the incorporation of [Tc-99m]Tc radiolabeled compounds ([Tc-99m]Tc-MA, [Tc-99m]Tc-MA-L-DOPA, [Tc-99m]Tc-MA-PLGA and [Tc-99m]Tc-MA-L-DOPA-PLGA) and the cytotoxicity of inactive compounds (MA and MA-L-DOPA compounds and encapsulated compounds (MA-PLGA and MA-L-DOPA-PLGA). Additionally, the biodistribution studies were carried out on healthy male Sprague-Dawley rats and a Parkinson's disease experimental model to evaluate the compounds' bioactivity using the radiolabeled compounds. The radiochemical yields of all radiolabeled compounds except [Tc-99m]Tc-L-DOPA-PLGA were above 95% and had stability over 6 h. The cytotoxic effects of all substances on SH-SY5Y and PC-12 cells increase with increasing concentration values. The uptake values of PLGA-encapsulated compounds are statistically significant in SH-SY5Y and PC-12 cells. The biodistribution studies showed that [Tc-99m]Tc-MA is predominantly retained in specific organs and brain regions, with notable uptake in the prostate, muscle, and midbrain. PLGA-encapsulation led to higher uptake in certain organs, suggesting its biodegradable nature may enhance tissue retention, and surface modifications might further optimize brain penetration. Overall, the results indicate that radiolabeled plant-derived encapsulated drug delivery systems with [99mTc]Tc hold potential as diagnostic agents for PD symptoms. This study contributes to the advancement of drug delivery agents in the field of brain research.