Serap Teksöz

Radiopharmaceutical model using 99m Tc-MIBI to evaluate amifostine protection against doxorubicin cardiotoxicity in rats

The aim of our study was to use anin vivo radiopharmaceutical model to investigate the cytoprotective effect of amifostine against doxorubicin-induced cardiotoxicity. Male Wistar rats were randomly divided into four groups (n = 6): 1) Saline (control); 2) Doxorubicin (DOX; 10 mg/ kg−1 intraperitoneally); 3) Amifostine (AMI; 200 mg/kg−1 intraperitoneally); 4) Doxorubicin plus amifostine (DOX + AMI). Amifostine was injected 30 minutes before doxorubicin in Group 4.99mTc-MIBI, 20 MBq/0.2 ml−1, was injected through the tail vein 72 hours after the drug administration. Rats were killed and samples of myocardium were removed by dissection 60 minutes after the injection of radiopharmaceutical. Radioactivity in each organ sample was counted using a Cd(Te) detector equipped with RAD 501 single-channel analyzer. The percent radioactivity was expressed as a percentage of the injected dose per gram of tissue (%ID/g−1). The %ID/g−1 activity was calculated by dividing the activity in each sample by the total activity injected and mass of each organ.99mTc-MIBI uptake as %ID/g−1 was 1.194 ± 0.502 and 0.980 ± 0.199 in the control and AMI groups, respectively. Doxorubicin administration resulted in a significant increase in %ID/ g−1 (3.285 ± 0.839) (p < 0.05). Amifostine administration 30 minutes before doxorubicin injection resulted a significant decrease in %ID/g−1’ (2.160 ± 0.791) (p < 0.05) compared with doxorubicin alone. The results showed that amifostine significantly attenuated doxorubicin-induced cardiotoxicity.

Labeling of famotidine with 99mTc and biodistribution studies on rats

Famotidine, a gastrointestinal drug was labeled with 99mTc and its radiopharmaceutical potential was observed on male Albino Wistar rats. Labeling yield was over 95%. Average specific activity and n-octanol/water partition coefficient (lipophilicity) were approximately 74 MBq/mg-0.66 GBq/mg and 3.4, respectively. Biodistribution studies were performed on Albino Wistar rats. The activity per gram tissue was calculated and time-activity curves were generated. The majority of the activity was observed in stomach, small intestines and kidneys. Liver and kidneys showed lower uptake compared to other H2-receptor rich tissues. Results show that 99mTc-famotidine is H2receptor specific.

Synthesis and Biological Evaluation of Bisphosphonate Compound Labeled with 99mTc(CO)3

In this study, radiolabeling of a bisphosphonate, alendronate (Alendronate sodium), was performed with the help of a bifunctional chelating agent. For that purpose, DTPA‐NHS (Diethylenetriaminepentaacetic acid dianhydride‐N‐hydroxysuccinimide) was synthesized with an esterification between DTPA and NHS. Combining the DTPA‐NHS ester with alendronate yields the DTPA‐Alendronate compound. The structure of synthesized compound was analyzed by 1H/13C/31P‐NMR and HPLC. After then, the labeling with [99mTc(CO)3]+ core of synthesized compound was provided. Performing quality controls of newly synthesized [99mTc(CO)3‐DTPA‐Alendronate] complex with thin layer radiochromatography (TLRC) and high‐performance liquid radiochromatography (HPLRC), the labeling yield was found as 99%. It was observed that the compound conserves its stability for 24 h in serum media. Biodistribution of the radiolabeled complex was performed on Wistar Albino rats to determine radiopharmaceutical potential of the [99mTc(CO)3‐DTPA‐Alendronate] complex. It is thought that the data gained from this study will contribute to the development of complexes with bisphosphonate.

Effect of rosemary (Rosmarinus officinalis) extract on the biodistribution of 99mTc sulphur colloid and on the radiolabeled blood constituents

With this study we evaluated the effects of the herb rosemary (Rosmarinus officinalis L. Lamiaceae) extract on the labeling of blood constituents with technetium-99m (99mTc) labeled sulphur colloid and on the biodistribution of 99mTc-Sulphur Colloid in Wistar albino rats. For this purpose, two groups of animals (male wistar rats, 130-140 g) were treated (1 mL) with a rosemary extract (750 mg/kg body wt.,n=9) and water (control, n=9) separately by gavage for five days. 99mTc-Sulphur Colloid was administrated by intravenous injection; organs/tissues were withdrawn and weighted. Blood was centrifuged, plasma and blood cells were isolated. The radioactivity was counted to calculate the percentage of activity per gram for each organ/tissue and percentage of activity in blood cells and plasma. A significant increase (p<0.05) in the uptake of 99mTc-Sulphur Colloid in the liver after the treatment with rosemary extract was observed. These results indicate that the substances or metabolites of the rosemary extract would change the biodistribution of 99mTc-Sulphur Colloid.

Synthesis, characterization and radiolabeling of folic acid modified nanostructured lipid carriers as a contrast agent and drug delivery system

Nanostructured lipid carriers (NLCs) are the new generation of solid lipid drug delivery systems. Their suitability as contrast agents for gamma scintigraphy is an attracting major attention. The aim of current study was to prepare surface modified nanostructured lipid carrier system for paclitaxel (PTX) with active targeting and imaging functions. In accordance with the purpose of study, PTX loaded nanostructured lipid carriers (NLCs) prepared, modified with a folate derivative and radiolabeled with technetium-99m tricarbonyl complex (99mTc(CO)3+). Cellular incorporation ratios of radiolabeled nanoparticles (99mTc(CO)3-PTX-NLC) were investigated in vitro on three cancer cell lines. Additionally in vivo animal studies conducted to evaluate biological behavior of 99mTc(CO)3-PTX-NLC on female Wistar Albino rats. Biodistribution results showed that the folate derivative modified 99mTc(CO)3-PTX-NLC had considerably higher uptake in folate receptor positive organs. The data obtained from present study could be useful in the design of biodegradable drug carriers of PTX and folate receptor based tumor imaging agents.

Determination of UO2(II), Th(IV) and Ce(III) Complexes Formed with Halogen and Nitro Derivatives of 8-Hydroxyquinoline

Proton-ligand stability constants for some iodo and nitro derivatives of 8-hydroxyquinoline were determined by Calvin Bjerrum potantiometric method. The stability constants of the corresponding chelates with UO2 (II), Th(IV) and Co(III) were studied potentiometrically at 25 °C by applying Irving-Rossotti computing method. The complexes of the nitro-substituted ligands were less stable than the corresponding complexes of the unsubstituted ligands. The stability constants of metal-ligands depend on the ionic radii and ionic charge of metals and also they decrease with steric repulsions of the nitro groups.

Stability constants of , Th4+ and Ce3+ with L-asparagine and thermodynamic parameters

The stability constants of L-asparagine and its complexes formed with , Th4+ and Ce3+ ions were determined potentiometrically using the Calvin–Bjerrum technique as adopted by Irving and Rossotti at different temperatures (290, 298 and 310 K), in 0.1 M KCl. The stability constants were computed using the least-squares treatment method in EXCEL program for proton–ligand and metal–ligand at the temperatures given above. The protonation constants of L-asparagine (log β2) were found to be 13.07 ± 0.01, 12.58 ± 0.10, 12.28 ± 0.16 at 290, 298 and 310 K, respectively. In addition, the thermodynamic parameters ΔH, ΔG and ΔS of L-asparagine and its complexes with metal ions were evaluated and discussed at the same temperatures.The stability constants of L-asparagine and its complexes formed with , Th4+ and Ce3+ ions were determined potentiometrically using the Calvin–Bjerrum technique as adopted by Irving and Rossotti at different temperatures (290, 298 and 310 K), in 0.1 M KCl. The stability constants were computed using the least-squares treatment method in EXCEL program for proton–ligand and metal–ligand at the temperatures given above. The protonation constants of L-asparagine (log β2) were found to be 13.07 ± 0.01, 12.58 ± 0.10, 12.28 ± 0.16 at 290, 298 and 310 K, respectively. In addition, the thermodynamic parameters ΔH, ΔG and ΔS of L-asparagine and its complexes with metal ions were evaluated and discussed at the same temperatures.

A new approach to liquid penetrant inspection: radiolabeled QDots

Penetrant technique is a sensitive non-destructive testing (NDT) method for detecting and locating the presence of cracks in sample surface. Today, NDT is used in a wide range of industries including aerospace, biotechnology, defence, marine, oil–gas and energy plants. This work focuses on potential use of radiolabeled ZnS coated CdTe quantum dots (QDots) as a penetrant for liquid penetrant testing. The synthesized QDots as a precursor were tested for surface defects detection in welded joints. The experimental results show the highest activities were found in defects on the sample surface. These finding are consistent with the sample NDT inspection test report.

Thymidine kinase enzyme selective imaging radiopharmaceutical: 99mTc(CO)3-Ganciclovir

Abstract The aim of this study is to radiolabel ganciclovir, known as having selective antiviral properties against thymidine kinase, with technetium tricarbonylcore (99mTc(CO)3+) and to investigate the biological behavior of this complex in vitro and in vivo. Commercially provided Ganciclovir (GCV) was radiolabeled with 99mTc(CO)3+. Initially, optimum radiolabeling conditions were determined by analyzing factors such as temperature, pH and time. Quality control of the radiolabeled compound was performed. The radiolabeling yield was found to be 97%. The 99mTc(CO)3-GCV complex also displayed good in vitro stability during the 24 h period. In vitro cell uptake studies showed that the 99mTc(CO)3-GCV complex is highly uptaken in A-549, PC-3, HeLa cell lines according to the control group 99mTc(I)-tricarbonyl core. The knowledge gained from in vivo and in vitro studies of 99mTc(CO)3-GCV could contribute to the development of a new HSV1-tk gene imaging agent.

Bioevaluation of 99mTc(CO)3–Guanine in vitro and in vivo

The aim of this study is to examine biological behaviour of radiolabeled guanine with [Tc(CO)3]+ core in vitro and in vivo. In vitro biological behavior of 99mTc(CO)3–Gua was evaluated on Lung (A-549), Breast (MCF-7), Colonic (Caco) carcinoma cell lines and normal human bronchial epithelial (NHBE). 99mTc(CO)3–Gua compound showed high uptake on A-549 cell line when compared to NHBE cell line. Biodistribution characteristics of 99mTc(CO)3–Gua was evaluated using New Zeland Rabbits. Scintigraphic results showed that a high level of radioactivity was observed in the lungs and liver shortly after administration of the 99mTc(CO)3–Gua and excretion takes place via both renal and hepatobiliary route. It was concluded that 99mTc(CO)3–Gua could be used as a nucleotide radiopharmaceutical for imaging purposes.