Makbule Asikoglu

Detecting inflammation with 131I-labeled ornidazole.

The aim of this study was to demonstrate the accumulation of 131I-labeled ornidazole (131I-ORN) in experimental abscesses. 131I-ORN was prepared by electrophilic radioiodination of ORN, using radioiodide in the presence of Iodogen. An in vivo inflammation model was prepared by intramuscular injection of turpentine into the thigh of rabbits. Four days later 131I-ORN was intravenously administered to rabbits. Serial scintigrams were performed at different periods, using a Sophy DX Gamma Camera. 131I-ORN was visualized at 10 min after injection. 131I-ORN was also administered intraperitoneally to rats with turpentine-induced inflammation, for quantitative biodistribution studies. Counts of selected tissues were taken by a NaI(Tl) scintillation detector (gamma counter) after rats were decapitated. The target-to-non-target muscle ratios were 2.5, 2.6, 2.9 and 1.9 at 1, 3, 5 and 24 h, respectively.

Microwave-assisted (radio)halogenation of nitroimidazole-based hypoxia markers

Microwave-assisted radiohalogenation for the production of short-lived radiopharmaceuticals has now been applied to the synthesis and radiolabelling of azomycin nucleosides. (Radio)halogens were incorporated either by nucleophilic substitution of a leaving group or by halogen-halogen exchange, in the synthesis of IAZA, IAZP and FAZA. A comparison of conventional labelling and microwave-assisted labelling procedures reflects a clear advantage of the microwave technique.

The rabbit biodistribution of a therapeutic dose of zoledronic acid labeled with Tc-99m.

The aim of the present study was to label a therapeutic dose of zoledronic acid (ZOL) with Tc-99m, evaluate its in vitro stability and compare its biodistribution to (99m)Tc-methylene biphosphonate ((99m)Tc-MDP) in normal rabbits. Preparation of 0.50 mg of (99m)Tc-ZOL was carried out by the reduction of (99m)Tc-pertechnetate in the presence of stannous chloride. The radiolabeling efficiency was found to be greater than 99%. The labeled complex was stable at least up to 6 h at room temperature determined by paper chromatography. (99m)Tc-ZOL and (99m)Tc-MDP were administered intravenously to the rabbits for scintigraphic studies. Between (99m)Tc-ZOL and (99m)Tc-MDP, there were no significant differences in the ratios of femur/BG and lumbar vertebrae/BG, whereas epiphysis/BG and the kidney/BG ratios of (99m)Tc-MDP were higher than (99m)Tc-ZOL at the static studies.

(99m) Tc-Doxycycline hyclate: a new radiolabeled antibiotic for bacterial infection imaging.

Radiolabeled antibiotics are promising radiopharmaceuticals for the precise diagnosis and detection of infectious lesions. Doxycycline Hyclate (DOX) was chosen to investigate new (99m) Tc-labeled antibacterial agent. Ready to use freeze dry kits were formulated with optimum labeling conditions. Human serum stability, sterility, and pyrogenicity of kits were estimated, and gamma scintigraphy, in vivo biodistribution, and histopathological studies with bacterial infected rats were performed. DOX were successfully labeled by (99m) Tc with high radiochemical purity, and the labeled compound was stable in human serum. Kits were sterile, pyrogen-free, and stable up to 6 months. Static images depicted rapid distribution throughout the body and high uptake in bacterial infected thigh muscle. The uptake ratios of radiopharmaceuticals in infected thigh muscle were found above 2 up to 5 h. Five hours after injection, the rats were sacrificed, and biodistribution was determined. Samples of bacterial infected muscle, healthy muscle, blood, liver, spleen, lung, kidney, stomach, intestine, urine and heart were weighed, and the radioactivity was measured by using a gamma counter. The %ID/g of (99m) Tc-DOX was found 0.23 ± 0.06 for infected thigh muscle. According to the imaging, biodistribution, and histopathological studies, the promising characteristics of (99m) Tc-DOX make the new radiopharmaceutical valuable to examine for future studies.

The Release of Isoconazole Nitrate from Different Suppository Bases: In-vitro Dissolution, Physicochemical and Microbiological Studies

The influence of the suppository base on the in‐vitro release of isoconazole nitrate was studied by dissolution, physicochemical diffusion and microbiological disk‐diffusion methods. Vaginal suppository formulations containing 25 mg isoconazole nitrate for local treatment of vaginitis were prepared by a fusion method, using different hydrophilic and lypophilic suppository bases (PEG 6000, PEG 4000, PEG 1500, Witepsol H15, Novata BD and Cremao). In‐vitro release rates were examined by dissolution, physicochemical diffusion and microbiological disk‐diffusion methods. In the physicochemical investigations the pH indicators (pH 1–14) erythrosin B, thymol blue, bromocresol green, chlorophenol red, phenol red, and alkali blue were added to agar gels. The discs were placed onto the agar gels and 21 h later, the coloured zone diameters were measured. In the microbiological investigations, the discs were put on the inoculated plates with the suspension of Candida albicans (Institute Pasteur 628). The inoculated plates were incubated at 37°C for 3 days, then the diameters of inhibition zones were measured.

The Absorption of 99mTc-alendronate Given by Rectal Route in Rabbits

Alendronate sodium (ALD) is a bisphosphonate medication used in the treatment and prevention of osteoporosis. Absorption of ALD as oral formulation is very poor (0.5%–1%). Its bioavailability can decrease with food effect. It has some gastrointestinal adverse effects such as gastritis, gastric ulcer, and esophagitis. The aim of this study was to develop a rectal formulation of ALD as an alternative to oral route and to investigate the absorption of it by using gamma scintigraphy. For this reason, ALD was labeled with Technetium-99m (99mTc) by direct method. The radiochemical characterization of the 99mTc-ALD was carried out by paper chromatography, thin layer chromatography, and electrophoresis methods. The labeling efficiency of 99mTc-ALD was found 99% without significant changes until 6 h postlabeling at room temperature. The rectal suppositories containing 99mTc-ALD were prepared by fusion method using polyethylene glycol (PEG) 1500. The 99mTc-labeled ALD suppositories were administrated to rabbits by rectal route. Serial scintigrams over all bodies of the rabbits were obtained at different time intervals using a gamma camera. We found that the rectal absorption of 99mTc-ALD from suppository formulation was possible. According to our results, this formulation of ALD can be suggested for the therapy of osteoporosis as an alternative route.

In vitro incorporation studies of 99mTc–alendronate sodium at different bone cell lines

Bisphosphonates can be labeled with Technetium-99m (99mTc) and are used for bone imaging because of their good localization in the skeleton and rapid clearance from soft tissues. Over the last decades bone scintigraphy has been used extensively in the evaluation of oncological patients to provide information about the sites of bone lesions, their prognosis and the effectiveness of therapy by showing the sequential changes in tracer uptake. Since the lesion visualization and lesion/bone ratio are important utilities for a bone scanning radiopharmaceutic; in this study incorporation of 99mTc labeled alendronate sodium (99mTc–ALD) was evaluated in U2OS (human bone osteosarcoma) and NCI-H209 (human bone carcinoma) cell lines. ALD was directly labeled by 99mTc, radiochemical purity and stability of the complex were analyzed by radioactive thin layer chromatography and radioactive high performance liquid chromatography studies. For cell incorporation study, NCI-H209 and U2OS cell lines were used with standard cell culture methods. The six well plates were used for all experiments and the integrity of each cell monolayer was checked by measuring its transepithelial electrical resistance (TEER) with an epithelial voltammeter. Results confirmed that ALD was successfully radiolabeled with 99mTc. 99mTc–ALD incorporated with NCI-H209 and U2OS cells. The uptake percentages of 99mTc–ALD in NCI-H209 and U2OS cell lines were found significantly different. Since 99mTc–ALD highly uptake in cancer cell line, the results demonstrated that radiolabeled ALD may be a promising agent for bone cancer diagnosis.

Evaluation of 99mTc-amoxicillin sodium as an infection imaging agent in bacterially infected and sterile inflamed rats

Bacterial infection is one of the major causes of morbidity and mortality especially in developing countries. The aim of this study was to develop a new radiopharmaceutical for imaging infection. The labeling conditions were optimized, and lyophilized kits were developed for instant preparing. The stability of 99mTc-AMOX in human serum was identified, sterility and pyrogenicity of the radiopharmaceutical were estimated, gamma scintigraphy and in vivo biodistribution with infected rats were investigated. The promising properties of 99mTc-AMOX combined with the development of reliable and instant lyophilized kit afford the opportunity of inflammatory process imaging.

Comparative permeability studies with radioactive and nonradioactive risedronate sodium from self-microemulsifying drug delivery system and solution

Abstract 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 mTc-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.

Radiolabeling and in vitro evaluation of 99mTc-methotrexate on breast cancer cell line

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.