Investigation of Radiolabeling Efficacy by Enhancement of the Chemical form of no Carrier Added 177Lu Isolated by Electro Amalgamation Process.

BACKGROUND: Due to the suitable nuclear decay characteristics, 177Lu is an attractive radionuclide for various therapeutic applications. The non-carrier added form of177Lu has drawn much attention because of its high specific activity needed in radiolabeling studies. There have been several separation methods for NCA177Lu production. OBJECTIVES: Among the various separation methods, the electro-amalgamation separation method has got a large potential for large scale production. Li presence is a significant problem in this separation method, which seriously affects the radiolabeling efficiency. METHODS: In this study, Li was separated from the final product of electro-amalgamation separation by adding an ion-exchange chromatography column to the separation process. RESULTS: NCA 177Lu was obtained by 84.09% ELM separation yield, 99.9% radionuclide purity and, 65 Ci/g specific activity. Then, 177Lu (177LuCl3 chemical form) was separated from Li using the ion exchange chromatography method by a separation yield of 94%. The obtained results of the radiolabeling efficacy studies showed that the radiochemical purity and radio-complex stability were significantly increased by separating NCA 177Lu from Li. CONCLUSION: This new separation setup consisting of two steps allows using 177Lu of such a favorable quality for labeling studies.

Neutronic and thermal-hydraulic analysis of fission molybdenum-99 production at Tehran Research Reactor using LEU plate targets.

Efficient and safe production of molybdenum-99 (99Mo) radiopharmaceutical at Tehran Research Reactor (TRR) via fission of LEU targets is studied. Neutronic calculations are performed to evaluate produced 99Mo activity, core neutronic safety parameters and also the power deposition values in target plates during a 7 days irradiation interval. Thermal-hydraulic analysis has been also carried out to obtain thermal behavior of these plates. Using Thermal-hydraulic analysis, it can be concluded that the safety parameters are satisfied in the current study. Consequently, the present neutronic and thermal-hydraulic calculations show efficient 99Mo production is accessible at significant activity values in TRR current core configuration.

Study of Bone Surface Absorbed Dose in Treatment of Bone Metastases via Selected Radiopharmaceuticals: Using MCNP4C Code and Available Experimental Data.

Bone metastases are major clinical concern that can cause severe problems for patients. Currently, various beta emitters are used for bone pain palliation. This study, describes the process for absorbed dose prediction of selected bone surface and volume-seeking beta emitter radiopharmaceuticals such as (32)P, (89)SrCl2,(90)Y-EDTMP,(153)Sm-EDTMP, (166)Ho-DOTMP, (177)Lu-EDTMP,(186)Re-HEDP, and (188)Re-HEDP in human bone, using MCNP code. Three coaxial sub-cylinders 5 cm in height and 1.2, 2.6, and 7.6 cm in diameter were used for bone marrow, bone, and muscle simulation respectively. The *F8 tally was employed to calculate absorbed dose in the MCNP4C simulations. Results show that with injection of 1 MBq of these radiopharmaceuticals given to a 70 kg adult man, (32)P, (89)SrCl2, and (90)Y-EDTMP radiopharmaceuticals will have the highest amount of bone surface absorbed dose, where beta particles will have the greatest proportion in absorbed dose of bone surface in comparison with gamma radiation. These results demonstrate moderate agreement with available experimental data.

Preliminary dosimetry of (166)Ho-propylene di-amino tetra (methy1enephosphonicacid) for human based on biodistribution data in rats.

CONTEXT: Nowadays, radionuclides with high ß- particle energies such as (166)Ho are recommended for bone marrow ablation in patients with multiple myeloma. The addition of skeletal targeted radiotherapy to the patients can improve the response rate in phase I and II trials, with promising long-term survival data. AIMS: In this work, the absorbed dose to each organ of human for (166)Ho-propylene di-amino tetra methy1enephosphonicacid (PDTMP) was evaluated based on biodistribution studies in rats and was compared with (166)Ho-tetraazacyclododecane tetramethylene-phosphonate (DOTMP) as the only clinically used Ho-166 bone marrow ablative agent. SETTINGS AND DESIGN: In this work, the accumulated activity in animals was extrapolated to the accumulated activity in humans by mass extrapolation method. The absorbed dose to each organ of human for (166)Ho-PDTMP was evaluated by medical internal radiation dose method. MATERIALS AND METHODS: In this study, 166 Ho-PDTMP complex was prepared successfully using an in-house synthesized PDTMP ligand and (166)HoCl 3. Radiochemical purity of (166)Ho-PDTMP was checked by instant thin layer chromatography (>99%). The biodistribution of (166)Ho-PDTMP in wild-type rats was checked in animal tissues up to 48 h. STATISTICAL ANALYSIS USED: All values were expressed as mean ± standard deviation, and the data were compared using Student's t-test. Statistical significance was defined as P < 0.05. RESULTS: The highest absorbed dose for this complex is observed in red marrow with 0.691 mSv/MBq. (166)Ho-PDTMP demonstrated a higher red marrow: Non target organ uptake ratio compared to (166)Ho-DOTMP. CONCLUSIONS: The results showed that 166 Ho-PDTMP has considerable characteristics compared to (166)Ho-DOTMP and therefore can be a good candidate for bone marrow ablation.

Evaluate of heavy metal concentration in shrimp (Penaeus semisulcatus) and crab (Portunus pelagicus) with INAA method.

The level of the heavy metal in green tiger shrimp (Penaeus semisulcatus) and crab (Portunus pelagicus) caught off the Persian Gulf near Bushehr province were investigated. This study was performed to evaluate instrumental neutron activation analysis (INAA) to analyze heavy metal concentration in crab and shrimp whole body tissue. The order of the swimmer crab and shrimp heavy metal concentrations were Zn>Fe>As>Mn>Co and Fe>Zn>Mn>As>Co, respectively. The results showed swimmer crab (Portunus pelagicus) and shrimp (Penaeus semisulcatus) caught off Persian gulf, were contaminated with high level of As (21.38±3.31ppm and 8.28±2.82 ppm, respectively). High levels of As and Mn were noted in crabs and shrimp, respectively.

A novel impedimetric nanobiosensor for low level determination of hydrogen peroxide based on biocatalysis of catalase.

A robust and effective nanocomposite film-glassy carbon modified electrode based on multi-walled carbon nanotubes and a room temperature ionic liquid 1-butyl-3-methylimidazolium hexafluorophosphate was prepared by a layer-by-layer self-assembly method. The fabricated modified electrode was used as a novel impedimetric catalase nanobiosensor for the determination of H(2)O(2). Direct electron transfer and electrocatalysis of catalase were fully investigated. The results suggested that catalase could be firmly adsorbed at the modified electrode. A pair of quasi-reversible redox peaks of catalase was observed in a 0.20 M degassed phosphate buffer solution of pH 7.0. The nanocomposite film showed a pronounced increase in direct electron transfer between catalase and the electrode. The immobilized catalase exhibited an excellent electrocatalytic activity towards the reduction of H(2)O(2). The electrochemical impedance spectroscopy measurements revealed that the charge transfer resistance decreases significantly after enzymatic reaction with hydrogen peroxide, so that the prepared modified electrode can be used for the detection of ultra traces of H(2)O(2) (5-1700 nM).

Preclinical evaluation of a new bombesin analog for imaging of gastrin-releasing peptide receptors.

Bombesin (BBN) is a peptide showing high affinity for the gastrin-releasing peptide receptor. Tumors such as prostate, small cell lung cancer, breast, gastric, and colon cancer are known to over express receptors to BBN and gastrin-releasing peptide (GRP). The goal of this study was to evaluate a new (67)Ga radiolabeled BBN analog based on the bifunctional chelating ligand DOTA (1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid), which could be used as a tool for diagnosis of GRP receptor-positive tumors. DOTA-GABA-BBN (7-14) NH(2) was synthesized using a standard Fmoc strategy. Labeling with (67)Ga was performed at 95°C for 30 minutes in ammonium acetate buffer (pH = 4.8). Radiochemical analysis involved ITLC and HPLC methods. The stability of radiopeptide was examined in the presence of human serum at 37°C up to 24 hours. The receptor-bound internalization and externalization rates were studied in GRP receptor expressing PC-3 cells. Biodistribution of radiopeptide was studied in nude mice bearing PC-3 tumor. Labeling yield of >90% was obtained corresponding to a specific activity of approximatrly 2.6 MBq/nmol. Peptide conjugate showed good stability in the presence of human serum. The radioligand showed a good and specific internalization into PC-3 cells (16.13% ± 0.71% at 4 hours). After 4 hours, a considerable amount of activity (52.42% ± 1.86%) was externalized. In animal biodistribution studies, a receptor-specific uptake of radioactivity was observed in GRP-receptor-positive organs. After 4 hours, the uptake in mouse tumor and pancreas was 1.30% ± 0.18% ID/g (percentage of injected dose per gram of tissue) and 1.21% ± 0.13% ID/g, respectively. These data show that [(67)Ga]-DOTA-GABA-BBN (7-14) NH2 is a specific radioligand for GRP receptor positive tumors and is a suitable candidate for clinical studies.

Adsorption of Ag, Cu and Hg from aqueous solutions using expanded perlite.

The aim of the present work was to investigate the ability of expanded perlite (EP) to remove of silver, copper and mercury ions from aqueous solutions. Batch adsorption experiments were carried out and the effect of pH, adsorbent dosage, contact time and temperature of solution on the removal process has been investigated. The optimum pH for the adsorption was found to be 6.5. Adsorption of these metal ions reached their equilibrium concentration in 120, 240 and 180 min for Ag (I), Cu (II) and Hg (II) ions, respectively. Experimental data were also evaluated in terms of kinetic characteristics of adsorption and it was found that adsorption process for these metal ions followed well pseudo-second-order kinetics. Using Langmuir isotherm model, maximum adsorption capacity of EP was found to be 8.46, 1.95 and 0.35 mg/g for Ag (I), Cu (II) and Hg (II) ions, respectively. Finally, the thermodynamic parameters including, the change of free energy (DeltaG degrees ), enthalpy (DeltaH degrees ) and entropy (DeltaS degrees ) of adsorption were calculated for each metal ion. The results showed that the adsorption of these metal ions on EP was feasible and exothermic at 20-50 degrees C.

SiRNA-mediated IGF-1R inhibition sensitizes human colon cancer SW480 cells to radiation.

PURPOSE: Insulin like growth factor receptor 1 (IGF-1R) is well-documented to play a key role in radiation response and tumor radiosensitivity, thus offering an attractive clinic drug target to enhance tumor sensitivity to anti-cancer radiotherapy. MATERIAL AND METHODS: Human colon carcinoma SW480 cells were transfected with the specific small interference RNA (siRNA) expression vector (pkD-shRNA-IGF-1R-V2) designed to target IGF-1R mRNA. The expression of IGF-1R mRNA and its protein among the transfected and untransfected cells were detected by semi-quantitative RT-PCR and ELISA assay. The changes in cell radiosensitivity were examined by MTT assay. RESULTS: Transfection of mammalian expression vector pkD containing IGF-1R siRNA was shown to reduce IGF-1R mRNA levels by up to 95%. ELISA assay detected a similar inhibition of IGF-1R protein levels in cells transfected with IGF-1R siRNA. SW480 cells transfected with the expression vector for siRNA significantly rendered cells more sensitive to radiation and the highest radiation enhancement ratio was 2.02 +/- 0.08. CONCLUSION: These data provide the first evidence that specific siRNA fragment (pkD-shRNA-IGF-1R-V2) targeting human IGF-1R mRNA is able to enhance colon cancer radiosensitivity. Also results indicated that, combining IGF-1R siRNA and radiation significantly enhances antitumor efficacy compared with either modality alone.

Knockdown of IGF-IR by RNAi inhibits SW480 colon cancer cells growth in vitro.

BACKGROUND AND AIMS: Colon cancer is the second leading cause of death due to cancer worldwide. Elevated expression of IGF-IR is a frequent genetic abnormality seen in this malignancy. The aim of the study was to examine the anti-growth effects elicited by a decrease in the protein level of IGF-IR by RNA interference (RNAi) in SW480 cells. METHODS: A plasmid-based polymerase III promoter system was used to deliver and express short interfering RNA (siRNA) targeting IGF-IR to reduce its expression in SW480 cells. The expression of IGF-1R protein was detected by Western blot. We assessed the effects of IGF-IR silencing on cancer cell growth by a growth curve. RESULTS: We prepared a type of IGF-IR short hairpin RNA (shRNA) expression vector that could efficiently inhibit the expression of IGF-IR in SW480 cells. At 48 h after transfection, the expression inhibition rate was 92 +/- 2% at mRNA level detected by RT-PCR analysis. Western blotting detected a similar inhibition of IGF-IR protein levels in cells transfected with pkD-shRNA-IGF-IR-V2. Downregulation of IGF-IR resulted in significant inhibition of cancer cell growth in vitro. The cell growth inhibition rates at 24, 48, and 72 h after pkD-shRNA-IGF-IR-V2 transfection were 32.06, 47.61, and 35.36%, respectively. CONCLUSIONS: Our data show that decreasing the IGF-IR protein level in SW480 cells by RNAi could significantly inhibit tumor growth in vitro, implying the therapeutic potential of RNAi on the treatment of colon cancer by targeting overexpression oncogenes such as IGF-IR. IGF-IR may be a potential therapeutic target for human colon cancer.