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Öğe Investigation of Bioactivity of Estragole Isolated from Basil Plant on Brain Cancer Cell Lines Using Nuclear Method(Bentham Science Publ Ltd, 2023) Avcibasi, Ugur; Dewa, Mouhaman Toukour; Karatay, Kadriye Busra; Kilcar, Ayfer Yurt; Muftuler, Fazilet Zumrut BiberBackground 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 radiolabeled with I-131 using the iodogen method. Quality control studies of the radiolabeled EST (I-131-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 with I-131 on human medulloblastoma (DAOY) and human glioblastoma-astrocytoma (U-87 MG) cell lines. Finally, the cytotoxicity of EST was determined, and cell uptake of I-131-EST was investigated on cancer cell lines by incorporation studies. Results As a result of these studies, it has been shown that I-131-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.Öğe Investigation of nanoformulation and incorporation potential of radiolabeled curcumin using HeLa and MDAH-2774 cells(Springer, 2021) Gokulu, Sevki Goksun; Kilcar, Ayfer Yurt; Bilgi, Ahmet; Karatay, Kadriye Busra; Yildirim, Nuri; Kayas, Cansu; Terek, Mustafa CosanNowadays plant origin compounds with anti-cancer properties come into prominence, among them is curcumin (CUR) with a remarkable anti-cancer activity against various cancers. CUR was nanoformulated (CUR-PLGA) by the polymer based poly(lactic-co-glycolic acid) (PLGA) and both CUR and CUR-PLGA were radiolabeled with iodine-131 radionuclide for investigation of their in vitro behaviour on Human cervix adenocarcinoma (HeLa) and Ovarian endometrioid adenocarcinoma (MDAH-2774) cell lines. The newly described radiolabeled CUR and CUR-PLGA may be initiative discovery of novel potential imaging and therapeutic agents.Öğe Isolation of resveratrol from peanut sprouts, radioiodination and investigation of its bioactivity on neuroblastoma cell lines(Springer, 2020) Karatay, Kadriye Busra; Kilcar, AyferYurt; Guldu, Ozge Kozgus; Medine, Emin Ilker; Muftuler, Fazilet Zumrut BiberRecently, natural antioxidant substances have been purified in a significant increasing incline from different plants for diagnosis and treatment options. in the current study, Resveratrol (RES) was isolated and radioiodinated with iodine-131 ([I-131]iodo-RES). Cell culture studies were conducted on neuroblastoma cells (SY-SH5Y and SK-N-AS) to investigate the bioavailability of [I-131]iodo-RES. the radioiodination yield of RES was 98.81 +/- 0.37% (n = 6). Uptake values up to 25% were observed notably on SK-N-AS cells until 24 h. Briefly; the current study will contribute to the development of novel radiolabeled plant origin agents for the imaging of neuroblastoma cells.Öğe Methanolic extract of Kigelia africana and wound healing: an in vitro study(Ma Healthcare Ltd, 2023) Karatay, Kadriye Busra; Muftuler, Fazilet Zumrut Biber; Law, Benedict; Aras, OmerObjective: Kigelia africana (Lam.) Benth. (Bignoniaceae) syn. Kigelia pinnata (Jacq. DC) is a tropical plant that is native to tropical Africa. The aim of this study was to determine if a methanolic extract prepared from Kigelia africana (KAE) can promote wound healing in treated human normal epidermal keratinocyte (HaCaT) cells and human normal foreskin fibroblast cell line (BJ) cells compared with untreated cells. Method: Experimental steps included: the methanolic extraction of the leaf and fruit of the Kigelia africana plant; the preparation of HaCaT and BJ cell lines; cell culture with a stable tetrazolium salt-based proliferation assay; and the evaluation of the wound healing effect of KAE (2 mu g/ml) in BJ and HaCaT cells. The phytochemical contents of KAE were determined using liquid chromatography quadrupole time-of-flight mass spectrometry. Results: The following molecules were identified as being present in the KAE, among others: cholesterol sulfate; lignoceric acid; embelin; isostearic acid; linoleic acid; dioctyl phthalate; arg-pro-thr; 15-methyl-15(S)-PGE1; sucrose; benzododecinium (Ajatin); and 9-Octadecenamide (oleamide). KAE effected faster wound healing in treated cells compared with untreated cells for both cell lines. HaCaT cells that had been mechanically injured and treated with KAE healed completely in 48 hours compared with 72 hours for untreated HaCaT cells. Treated BJ cells healed completely in 72 hours compared with 96 hours for untreated BJ cells. Concentrations of KAE up to 300 mu g/ml had a very low cytotoxic effect on treated BJ and HaCaT cells. Conclusion: The experimental data in this study support the potential of KAE-based wound healing treatment to accelerate wound healing.Öğe mTOR inhibitors from a diagnostic perspective: radiolabeling of everolimus and its nanoformulation, in vitro incorporation assays against cervix and ovarian cancer cells(Springer, 2022) Bilgi, Ahmet; Kilcar, Ayfer Yurt; Gokulu, Sevki Goksun; Kayas, Cansu; Yildirim, Nuri; Karatay, Kadriye Busra; Akman, LeventmTOR inhibitors are recently important tools for cancer treatment. They act on cell growth regulation, proliferation, and survival. Pharmacological therapy with mTOR inhibitors such as everolimus is emerging as an alternate approach. Meanwhile, early diagnosis is a hot target in cancer research. Conversely, it can be a novel diagnosis approach to monitor mTOR inhibitors during their pathway. From this point of view, radiolabeling of everolimus and its nanoformulation (EVE-PLGA nanoparticles) in high yields (95%) with an important diagnostic radionuclide (technetium-99m) is described. Besides, in vitro incorporation assays of radiolabeled everolimus and its nanoformulation against the cervix and ovarian cancer cells were demonstrated 8- and 12-times high values than control group. In conclusion, radiolabeled everolimus and its nanoformulation have a promise to improve on monitoring mTOR inhibitors.Öğe A novel SPECT/MRI bimodal imaging probe: Tc-99m-DPAPA-Fe3O4 nanoconjugate(Springer, 2023) Yasakci, Volkan; Tutun, Elif; Karatay, Kadriye Busra; Aras, Omer; Unak, PerihanThis study aimed to create a novel bimodal probe. For this purpose, cubic iron oxide nanoparticles (C-Fe3O4 NPs) conjugated with an EDTMP derivative called DPAPA thought to be a targeting tool for prostate cancer and bone metastases were studied. NPs were synthesized and conjugated with DPAPA, and then characterization studies were carried out. The particles were demonstrated to be cubic shaped, with an average size of 68.55 +/- 1 0.03 (n = 3) nm. Then the nanoconjugates were radiolabeled with Tc-99m. In vitro cellular affinities were conducted using PC-3, RWPE-1, LNCaP, K562, and Saos-2 cell lines. In conclusion, radio-nanoconjugates have the potential for bimodal MRI/SPECT imaging.Öğe Polymer Coated Iron Nanoparticles: Radiolabeling & In vitro Studies(Bentham Science Publ Ltd, 2021) Yilmaz, Selin; Ichedef, Cigdem; Karatay, Kadriye Busra; Teksoz, SerapBackground: 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 targeted Tc-99m 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 with Tc-99m. 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 deter- mined 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: Tc-99m 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 super-paramagnetic characteristicsÖğe Radioiodination of Pimonidazole as a Novel Theranostic Hypoxia Probe(Bentham Science Publ Ltd, 2021) Inci, Ilknur Demir; Tekin, Volkan; Kilcar, Ayfer Yurt; Guldu, Ozge Kozgus; Medine, Emin Ilker; Karatay, Kadriye Busra; Dervis, EmineBackground: Tumors are defined as abnormal tissue masses, and one of the most important factors leading to the growth of these abnormal tissue masses is Vascular Endothelial Growth Factor, which stimulates angiogenesis by releasing cells under hypoxic conditions. Hypoxia has a vital role in cancer therapy, thus it is important to monitor hypoxia. The hypoxia marker Pimonidazole (PIM) is a candidate biomarker of cancer aggressiveness. Objective: The study aimed to perform radioiodination of PIM with Iodine-131 (I-131) to join a theranostic approach. For this purpose, PIM was derived as PIM-TOS to be able to be radioiodinated. Methods: PIM was derived via a tosylation reaction. Derivatization product (PIM-TOS) was radioiodinated by using iodogen method and was analyzed by High-Performance Liquid Chromatography and Liquid chromatography-mass spectrometry. Thin layer radiochromatography was utilized for its quality control studies. Results: PIM was derived successfully after the tosylation reaction. The radioiodination yield of PIM-TOS was over 85%. Conclusion: In the current study, radioiodination potential of PIM with I-13(1), as a potential theranostic hypoxia agent was investigated. Further experimental studies should be performed for developing a novel hypoxia probe including theranostics approaches.Öğe Radiolabeling of Zonisamide for a Diagnostic Perspective(Bentham Science Publ Ltd, 2024) Dervis, Emine; Karatay, Kadriye Busra; Durkan, Kubra; Kilcar, Ayfer YurtObjective: Epilepsy is one of the oldest and the most common chronic neurological diseases. Antiepileptic drugs (AEDs) are the backbone of epilepsy treatment. However, epileptogenesis has not been fully elucidated. One of the critical reasons for this is the lack of reliable biomarkers. Neuroimaging suggests a non-invasive examination and investigation tool that can detect critical pathophysiological changes involved in epileptogenesis and monitor disease progression. In the current study, the radiolabeling potential of Zonisamide (ZNS) (the secondgeneration AED) with Technetium-(99m) (Tc-99m) is examined to neuroimage the epileptogenic processes by contributing to the development of potential radiotracers. Methods: ZNS was labeled with Tc-99m and the radiochemical yield of [Tc-99m]Tc-ZNS was determined with TLRC (Thin Layer Liquid Radio Chromatography and HPLRC (High Performance Liquid Radio Chromatography) radiochromatographic methods. In vitro behavior of [Tc-99m]Tc-ZNS was determined with time-dependent uptake of [Tc-99m]Tc-ZNS on the SHSY5Y human neuroblastoma cells. Results: The radiochemical yield of [Tc-99m]Tc-ZNS was determined as 98.03 +/- 1.24% (n = 6) according to radiochromatographic studies results. [Tc-99m]Tc-ZNS demonstrated 5.38 and 6.18 times higher uptake values than the control group on the human neuroblastoma SH-SY5Y cell line at 120 and 240 minutes, respectively. Conclusion: This study showed that the current radiolabeled antiepileptic drug has a diagnostic potential to be used in imaging neurological processes.Öğe Synthesis and in vitro evaluation of 99mTc radiolabeled lapatinib (LPT) and its PLGA formulation(Springer, 2024) Gokulu, Sevki Goksun; Karatay, Kadriye Busra; Bilgi, Ahmet; Kayas, Cansu; Yildirim, Nuri; Kilcar, Ayfer Yurt; Muftuler, Fazilet Zumrut BiberLapatinib-(LPT) is a dual tyrosine kinase inhibitor that has important effects on the targeted therapy of various tumours. The current study is aimed to use a novel tracer strategy including Technetium-99 m-(Tc-99m) radiolabeled LPT and its poly(lactic-co-glycolic acid)-(PLGA) encapsulated formulation-(LPT-PLGA). In vitro bioaffinity of the [Tc-99m]Tc-LPT and [Tc-99m]Tc-LPT-PLGA was evaluated by using cell culture methods on human breast adenocarcinoma (MDA-MB-231), cervix adenocarcinoma and human ovarian (MDAH-2774) cancer cell lines. Radiochemical yield were over 95% and both compounds were examined high incorporation values on HeLa and MDAH cell lines. Current results may contribute to develope as the encapculated agents including radiotracer.Öğe 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(Springer, 2024) Uygur, Emre; Karatay, Kadriye Busra; Dervis, Emine; Evren, Vedat; Kilcar, Ayfer Yurt; Guldu, Ozge Kozgus; Sezgin, CerenParkinson'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.Öğe The radiolabeling of [161Tb]Tb-PSMA-617 by a novel radiolabeling method and preclinical evaluation by in vitro/in vivo methods(Springer, 2024) Uygur, Emre; Sezgin, Ceren; Parlak, Yasemin; Karatay, Kadriye Busra; Arikbasi, Bilal; Avcibasi, Ugur; Biber Muftuler, Fazilet ZumrutProstate 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.
