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Radiolabeled trastuzumab (TRZ) loaded solid lipid nano-particles (SLNs) were prepared by high shear homogenization and sonication techniques. The apoptosis mechanism of TRZ-SLNs was studied only with the MCF-7 cell line, while the cytotoxicity and cell binding capacity were investigated using breast cancer cells (MCF-7 and MDA-MB-231) and the human keratinocyte cell line (HaCaT). The particle sizes of TRZ-SLNs were found to be below 100 nm, and they possessed a negative charge. The high radiolabeling efficiency and good radiolabeling stability in saline and a cell culture medium were obtained in the results of radiolabeling studies. According to the in vitro studies, TRZ-SLNs were found to be biocompatible, and they effectively induced apoptosis in MCF-7 cells. After the parenteral injection of TRZ-SLNs into rats, a sustained release profile in blood circulation was achieved compared with free drug solution by the evaluation of pharmacokinetic parameters. As a conclusion, the study reveals that Technetium-99m (Tc-99m radiolabeled) TRZ loaded SLN formulations could be promising theranostic agents based on their characterization profiles, in vitro cellular uptake and apoptosis induction capacity, and in vivo pharmacokinetic profiles., Cost Action [CA-17104], We would like to give our thanks to Ege University Planning and Monitoring Coordination of Organizational Development and Directorate of Library and Documentation for their editing and proofreading service for this study. This research was supported by Cost Action (grant CA-17104) .

Today, the most important treatment methods for cancer are chemotherapy, surgical intervention, and radiotherapy. In recent years, many studies on radioimmunotherapy have been carried out. New drugs and treatment strategies are constantly being researched, and targeted cancer therapy is the treatment with the highest efficacy and negligible side effects compared to other methods. Breast cancer is the most common type of cancer in women. Human epidermal growth factor receptor 2 (HER2) is overexpressed in 20-30% of breast cancer cases. Trastuzumab is a humanized monoclonal antibody of recombinant DNA origin targeting the HER2 protein. In this study, the pharmaceutical part of a new radiopharmaceutical to be used in breast cancer treatment was prepared. For this purpose, molecular insertion studies were conducted to show the binding sites between Trastuzumab and different chelating agents (DOTA, DTPA, EDTA and MAG3) in silico. Then, these chelating agents were complex, and characterization studies were carried out.

Aim: Exendin-4 is a type 2 diabetes antidiabetic drug that is a peptide agonist of the glucagon-like peptide 1 receptor (GLP-1R). Up to date, different exendin-4 compounds have been radiolabeled with many radioisotopes such as 68Ga, 18F, 64Cu and 99mTc for various purposes like study of over expression of GLP-1R in insulinoma. The purpose of this study is to radiolabel exendin-4 with 99mTc under appropriate conditions. Methods: In this study, exendin-4 was labeled with 99mTc, and quality control tests of 99mTc-exendin-4 were done using ascending radioactive thin layer chromatography (RTLC). Also, the effects of important parameters such as the amount of reducing agent, pH value, incubation time, and radiation dose on the labeling efficiency were investigated. Then, the stability of 99mTc-exendin-4 was assessed. Results: According to the results, 99mTc-exendin-4 was prepared with over 95 percent labeling efficiency by a novel, easy, and quick direct method with 30-min incubation time at pH 6.6. To achieve the best radiolabeling condition; 10 µg of exendin-4, 50 µg of stannous chloride (reducing agent) and 37 MBq 99mTc was used. The RTLC studies indicated that 99mTc-exendin-4 is stable up to 6 h in room temperature. Conclusion: The obtained results demonstrated that radiolabeled exendin-4 may be a promising agent for GLP-1R imaging studies. Further studies are in progress in order to evaluate receptor binding capacity and biodistribution of the complex in experimental animals.

As humans are exposed to radiation from various sources in almost every area of life, effects of radiation on human health have been an important subject of research. Starting with the discovery of X-rays, studies in this field were accelerated by pivotal developments such as nuclear warfare (atomic bombings of Hiroshima and Nagasaki) and reactor accidents (the Chernobyl disaster). Type of radiation exposure and exposure time and dose have been determined to be the primary factors, while ionizing radiation has been proven to have more serious effects than does non-ionizing radiation. While ionizing radiation can lead to cancer development, non-ionizing radiation does not have carcinogenic effects shown by long-term studies. In this review, we compiled information about the effects of radiation on human health., İnsanlar hayatın hemen her alanında birçok kaynak nedeniyle radyasyona maruz kaldıklarından, radyasyonun insan sağlığı üzerindeki etkileri önemli bir araştırma konusu olagelmiştir. X ışınlarının keşfinin ardından, nükleer savaş (Hiroşima ve Nagazaki atom bombası saldırıları) ve reaktör kazaları (Çernobil felaketi) gibi belirleyici gelişmelerle bu alandaki çalışmalar hız kazanmıştır. Maruz kalınan radyasyon türü, dozu ve maruziyet süresinin başlıca faktörler olduğu tespit edilmiş ve iyonize radyasyonun non-iyonize radyasyona kıyasla daha ciddi etkilere sebep olduğu kanıtlanmıştır. İyonize radyasyon kanser oluşumuna neden olabilmekteyken, non-iyonize radyasyonun uzun dönem çalışmalarla kanıtlanmış karsinojenik etkileri söz konusu değildir. Bu çalışmada radyasyonun insan sağlığı üzerindeki etkilerine dair bilgiler derlenmiştir.

The cancer is serious health problem and leading cause of death in the world. There have intensively studied for diagnosis and therapy of this disease and these studies provided important insights into their mechanism of action and therapeutic/diagnostic effects. The accurence rates of cancer has dramatic increase, particularly in the developed countries. Although there are many different strategies about diagnosis and treatment for cancer, more effective new approaches are needed. In this review, we summarize recent developments on cancer diagnosis, radiopharmaceuticals in cancer diagnosis, nanoparticulate systems in cancer diagnosis, T cells in cancer diagnosis, cancer therapy and pharmacokinetic of anticancer drugs. We thought that while there are some current limitations such as clinical studies, ranging from diagnosis to theraphy, future improvements in cancer diagnosis and treatment will meet the most relevant issues required for the eventual approval of nano-drugs, radiopharmaceuticals, T cells in clinical practice.

Monte Carlo simulation method and Nuclear Medicine MIRD method were used to evaluate the effect of ra-diopharmaceuticals on Covid-19 disease. The mean absorbed organ dose in the target organ and gamma radi-ation emitter attenuation properties such as linear attenuation coefficients, energy absorption build-up factors (EABF), exposure build-up factors (EBF), and relative dose distributions (RDD) were examined. The results showed that radiopharmaceuticals containing gamma radiation emitters which are densely ionizing charged particles induced membrane damage and produced protein damage.

Cancer is one of the most important burdens for the health systems worldwide due to cancer-related deaths associated with late diagnosis and treatment toxicities. Diagnosis of cancer plays a critical role in reducing cancer death rates as it facilitates early prognosis and treatment. Current cancer treatment mainly includes the resection of tumor tissue, radiation treatment, and pharmaceutical treatment. Although various techniques, methods, and drugs are clinically used in cancer diagnosis and treatment, they are inadequate for early diagnosis and effective treatment. Therefore, several studies regarding cancer-targeted nanosized drug delivery systems and theranostic approach are performed. Nanovesicular systems, one of the most important types of drug delivery systems, are formulated for the effective delivery and controlled release of active compounds such as drugs, genes, phytocompounds, and imaging agents. In this chapter, different types of nanovesicles are reviewed after providing information about conventional cancer imaging and treatment. Furthermore, targeting mechanisms of nanovesicles for cancer are explained. Finally, some studies performed to develop the nanovesicles as the imaging, treatment, or theranostic system for cancer are summarized. © 2022 Elsevier Inc. All rights reserved.

Infection is one of the important burdens on the health care system, not only due to leading morbidity and mortality but also because of the development of antibiotic resistance. Although the infection can be diagnosed by imaging techniques, more effective agents including radiopharmaceuticals may be required to image deep-seated infections. Imaging also plays a critical role in the choosing of optimum treatment options and following treatment. Theranostic agents offer many advantages such as monitoring the biodistribution and targeting of therapeutic agents, as well as rapid diagnosis and treatment. Colistin, a cationic peptide, leads to bacterial death through interaction with lipopolysaccharides in the cell wall of bacteria. In our study,177Lu as radionuclide part and colistimethate sodium (a prodrug of colistin, CMS) as pharmaceutic part were chosen to prepare a radiopharmaceutical for imaging and treatment of infections.177Lu-CMS complex was formed under room condition, and radiolabeling efficiency was determined by paper and high-performance liquid chromatography. The effect of the filtration process on radiolabeling was evaluated among the labeling efficiencies of filtered and un-filtered complexes. The different incubation times (5, 30, and 60 min) effect on the radiolabeling process was also evaluated. Moreover, in vitro stability of177Lu-CMS complex in saline solution was assessed during 7 days. According to the results, desired radiolabeling efficiency was not obtained under tested conditions and stability studies. Therefore, various modifications such as the addition of chelating agents or stabilizers in the radiolabeling procedure should be made to increase the radiolabeling stability. Further studies regarding radiolabeling are surely needed, and our studies are continuing. © 2022 Marmara University Press.

Fluorodeoxyglucose (FDG), marked with the most used Positron Emission Tomography (PET) radiopharmaceutical Fluorine-18 (F-18), is a glucose analog and is taken to living cells through membrane glucose carriers. F-18 FDG involvement in tissue is proportional to glucose use. In many cancers, there is increased glucose use due to increased gluten expression and hexokinase activity. F-18 FDG PET is a proven method for diagnosis, staging, re-staging, and evaluation of treatment response in oncology. The purpose of this study is to find the effect of ionizing radiation on proteins in the mechanism of action of FDG and determine to Molecular mechanisms of F-18 FDG accumulation in metabolism. In the study, two different models were used together, the first method, the study was Molecular Docking method for modeling molecules deconstructed and the structure of FDG was energy minimized by utilizing the density functional theory, and the B3LYP functional was used with 6-311G basis set. The second method was the Monte Carlo method for modeling ionizing radiation interactive with the potential routes of FDG metabolism within the cell. It was determined that the Gibbs free energy (?G) change was compatible with the ionizing radiation factors for binding of FDG to the aphthous regions of Glucose-6-phosphate isomerase (G1), hexokinase (G2), and glucose transporter-1 (G3) were selected. In this study, the strong binding of FDG to protein influences the effect of radiation on the active site of enzymes. The G1 and G3 shown in the study interacted with only one charged amino acid FDG, and the absence of an aromatic residue around it can be considered among the results of this study as the cause of the low protective effect against ionizing radiation. © 2022 Elsevier Ltd, None.

The clinical impact and accessibility of Tc-99m tracers for cancer diagnosis would be greatly enhanced by the availability of a new, simple, and easy labeling process and radiopharmaceuticals. in this study, Technetium-99m-imatinib mesylate ([Tc-99m]TcIMT) was developed and prepared as a new radiopharmaceutical for breast cancer diagnosis. the effect of critical process parameters on the product quality and stability of [Tc-99m]TcIMT was investigated using the quality by design concept of the ICH Q8 (Pharmaceutical Development) guideline. [Tc-99m]TcIMT was subjected to in vitro cell binding studies to determine healthy and cancer cell affinity using HaCaT and MCF-7 cells, respectively. the optimal radiolabeling procedure with 1 mg of IMT, 500 mu g of stannous chloride, 0.1 mg of ascorbic acid, and (1m)Ci Tc-99m radioactivity was obtained for [Tc-99m]TcIMT. the pH of the reaction mixture was adjusted to 10 and allowed to react for 15 min at room temperature. the radiochemical purity of [Tc-99m]TcIMT was found to be higher than 90% at room temperature up to 6 h. Chromatography analysis revealed >85% [Tc-99m]Tc1MT complex formation with promising stability in saline, cell medium, and serum up to 6 h. the radiolabeled complex showed a higher cell-binding ratio to MCF-7 cells (88.90% +/- 3.12) than HaCaT cells (45.64 +/- 4.72) when compared to Tc-99m. Our findings show that the developed preparation method for [Tc-99m]TcIMT falls well within the proven acceptable ranges. Applying quality by design (QbD) principles is feasible and worthwhile for the preparation of [Tc-99m]TcIMT. in conclusion, radiochemical purity, stability, and in vitro cell binding evaluation of the [Tc-99m]TCIMT complex indicate that the agent can be utilized for imaging of breast cancer cells., T.R. Prime Ministry State Planning Organization FoundationTurkiye Cumhuriyeti Kalkinma Bakanligi [09/DPT/001]; COST (European Cooperation in Science and Technology) ActionEuropean Cooperation in Science and Technology (COST) [CA17104], The authors would like to thank the T.R. Prime Ministry State Planning Organization Foundation (project number: 09/DPT/001). the authors would like to thank the COST (European Cooperation in Science and Technology) Action (project number: CA17104). the authors would like to acknowledge the support of Ege University Nuclear Medicine Department in obtaining the 99mTc radionuclide.

OBJECTIVE The purpose of this study was to develop lipid-water based drug delivery system of Alendronate Sodium (ALD) in liquid and solid form obtained by using spray drying method and compare these two forms with radioactive cell culture studies. METHODS This study included the development of liquid and solid form obtained by spray drying method, radiolabelling of ALD with 99mTc, preparation of formulations containing 99mTc -ALD and evaluation of their permeability with Caco-2 cell. The liquid formulations have been developed by using various surfactants, co-surfactants, oil and water phases. Physicochemical characterizations like droplet size, polydispersity index (PDI) and zeta potential measurements and short term stability studies were investigated. RESULTS According to the measurement results, two oil in water formulations (F1-L and F2-L) were selected and spray dried with Buchi mini spray dryer apparatus to provide solid formulations (F1-S and F2-S). ALD was labeled with 99mTc and added to formulations. The effect of experimental conditions on radiolabeling efficiency of ALD and stability of all formulations containing 99mTc-ALD were investigated through Radio Thin Layer Chromatography (RTLC). It was observed that the labeling efficiency of ALD was greater than 90% and all formulations were found to be stable up to 6 h at room temperature. Permeability of radiolabeled ALD from all formulations was performed by using Caco-2 cells. According to the cell culture studies, permeability from spray dried formulations of ALD was found higher than liquid formulations. CONCLUSION As a conclusion, spray dried formulations could be a promising drug delivery system for enhancing the permeability of ALD. Furthermore, this study is a good example of the use of radiolabeled compounds in drug development.

Microemulsions have been used increasingly for last year’s because of ideal properties like favorable drug delivery, ease of preparation and physical stability. They have been improved the solubility and efficacy of the drug and reduce the side effects. Use of radiolabeled microemulsions plays an alternative role in drug delivery systems by investigating the formation, stability and application of microemulsions in radiopharmacy. Gama scintigraphic method is well recognized for developing and detecting the biodistribution of newly developed drugs or formulation. This review will focus on how radionuclides are able to play role with characterization studies of microemulsion drug delivery systems.

In many disease states, functional changes occur or become visible before anatomical changes. Nuclear medicine examines function, rates of metabolism, and various other physiological activities within the body, rather than focusing primarily on anatomy and structure. So, this technique can often provide significant information such as early detection and extent of disease. Cancer has been one of the major social and health concerns for the last 10 decades. For many cancer types, early diagnosis could reduce mortality. The diagnosis of tumors and monitoring of therapy in many patients rely mainly on morphological imaging techniques such as CT, ultrasound (US), MRI, and X-ray imaging that predominantly offer anatomical information. However, functional imaging modalities such as single-photon emission computed tomography (SPECT) and positron-emission tomography (PET) have a great impact on patient management by providing tools for a better staging of the disease, visualization of the tumor, and evaluation of eligibility for treatment. Tumor staging is an essential part of cancer management, as it determines treatment options and prognosis. Molecular imaging is the visualization, characterization, and measurement of biological processes at the molecular and cellular levels in humans and other living systems. Molecular imaging can facilitate early diagnosis, can identify the stage of disease, can provide fundamental information on pathological processes, and can be applied to follow the efficacy of therapy. Molecular imaging using high-resolution SPECT and PET has advanced elegantly and has steadily gained importance in the clinical and research areas. This chapter briefly summarizes the state of nuclear medicine and radiopharmaceuticals for molecular diagnosis.

Cationic nanoparticles of CS were developed according to ionotropic gelation process as potential cancer cell targeting agent. CS nanoparticles (CSNP) (F1 and F2) diameters varied between ranges of 100–800 nm. Particle size, polydispersity index and zeta potential values of formulations were measured by photon correlation spectroscopy. The morphological analysis for CSNPs was provided with scanning electron microscopy. For cell incorporation study, F1 and F2 were directly labeled by Technetium-99m ( 99m Tc), radiochemical purity and stability of the complex were analyzed by radioactive thin layer chromatography and radioactive high performance liquid chromatography studies. After that, incorporation of 99m Tc labeled F1 and F2 were evaluated in U 2 OS and NCI–H209 cell lines. The six well plates were used for all experiments and the integrity of each cell monolayer was checked by measuring its TEER values with an epithelial voltammeter. Results confirmed that F1 and F2 formulations were successfully radiolabeled with 99m Tc. The incorporation percentages of 99m Tc labeled F1 and F2 in NCI–H209 and U 2 OS cell lines were found different when they compared to 99m Tc solution. Since 99m Tc labeled F1 and F2 highly uptake in cancer cell line. The results demonstrated that radiolabeled CSNPs may be a promising agent for cancer diagnosis.

In the present study 99mTc-MTX was prepared with high labeling yield by a new simple and easy formulation method. According to cell culture studies, 99mTc-MTX incorporated with both MCF-7 and CRL8798 cells, with significant differences in the uptake percentages. Since 99mTc-MTX highly uptake in cancer cell line, the results demonstrated that radiolabeled MTX may be promising for breast cancer diagnosis of oncological patients.

The purpose of this work is to prepare a self-microemulsifying drug delivery system (SMEDDS) for risedronate sodium (RSD) and to compare the permeability with RSD solution. The solubility of RSD was determined in different vehicles. Phase diagrams were constructed to determine the optimum concentration of oil, surfactant, and cosurfactant. RSD SMEDDS was prepared by using a mixture of soybean oil, cremophor EL, span 80, and transcutol (2.02:7.72:23.27:61.74, w/w, respectively). The prepared RSD SMEDDS was characterized by droplet size value. In vitro Caco-2 cell permeability studies were performed for SMEDDS and solution of radioactive ((99 m)Tc-labeled RSD) and nonradioactive RSD. The experimental results indicated that RSD SMEDDS has good stability and its droplet size is between 216.68 ± 3.79 and 225.26 ± 7.65 during stability time. In addition, RSD SMEDDS has higher permeability value than the RSD solution for both radioactive and nonradioactive experiments. The results illustrated the potential use of SMEDDS for delivery of poorly absorbed RSD.