The purpose of this research study is to prepare Exametazime (d,l-HMPAO) kit for labeling with 99m-technetium radionuclide as a brain perfusion diagnostic system. In first step, the active pharmaceutical ingredient d,l-HMPAO was prepared in two steps with the purity of 99.29 %. Its molecular structure was characterized using elemental analysis, Fourier-transform infrared spectroscopy (FT-IR) and nuclear magnetic resonance (NMR) technique. In second step, the d,l-HMPAO kit was prepared using six different formulations and labeled by technetium-99m radionuclide. The high radiochemical yield was attributed to the high amount of SnCl2 and adding phosphate buffer. The animal studies were conducted on three-month old male Wistar rats. The biodistribution studies revealed that, the mean activity in brain of all rats was above 1% ID/g. This showed the high isomerism purity of the synthesized compound (d,l-HMPAO) and optimization of the suggested formulations.

Introduction. Reducing human error is an important factor for enhancing safety protocols in various industries. Hence, analysis of the likelihood of human error in nuclear industries such as radiopharmaceutical production facilities has become more essential. Methods. This cross-sectional descriptive study was conducted to quantify the probability of human errors in a ⁹⁹Mo/^99mTc generator production facility in Iran. First, through expert interviews, the production process of the ⁹⁹Mo/^99mTc generator was analyzed using hierarchical task analysis (HTA). The standardized plant analysis risk-human (SPAR-H) method was then applied in order to calculate the probability of human error. Results. Twenty tasks were determined using HTA. All of the eight performance shaping factors (PSF_S) were evaluated for the tasks. The mean probability of human error was 0.320. The highest and the lowest probability of human error in the ⁹⁹Mo/^99mTc generator production process, related to the ‘loading the generator with the molybdenum solution’ task and the ‘generator elution’ task, were 0.858 and 0.059, respectively. Conclusion. Required measures for reducing the human error probability (HEP) were suggested. These measures were derived from the level of PSF_S that were evaluated in this study.

A variety of new silica–zirconia sulfate inorganic polymer sorbent materials, designated as SZ were prepared using the in situ generated zirconium-tetra octanoxide Zr(Oct)₄ from condensation of zirconium-tetra-n-butoxide and 1-octanol followed by reaction with tetraethylorthosilicate in ethanolic solution by sol gel method. The prepared SZ sorbents were characterized by FT-IR, SEM, XRD, N₂ sorption isotherms and ICP techniques. Different molar ratios of substrates were used in order to study the maximum capacity of MoO₄ ²⁻ adsorption. Mo adsorption was found to depend on several parameters such as SO₄ ²⁻/Zr, Zr/Si molar ratios and gel calcination temperatures. The maximum amount of ⁹⁹Mo (Mo) adsorption on inorganic polymer was realized to be about 450 mg/g. Notably, elution of technetium-99m with a small volume of saline solution was carried out with about 75 % yield and less than 0.02 % ⁹⁹Mo breakthrough.

Background

Recurrence in hepatocellular carcinoma (HCC) after conventional treatments is a big challenge. Despite the promising progress in advanced targeted therapies, HCC is the fourth leading cause of cancer death worldwide. Radionuclide therapy could be an effective targeted approach to address this concern. Rhenium-188 (¹⁸⁸Re) is a β-emitting radionuclide that can be used in clinic for apoptosis induction and inhibit cell proliferation. Although adherent cell cultures are efficient and reliable, the lack of appropriate cell-cell and cell-ECM contact exists. It has been demonstrated that three-dimensional organotypic human cancer models are suitable alternatives.

Methods

Conventional adherent culture and 3D constructs of Huh7 or HepG2 hepatoma cell lines cultured on liver extracellular matrix (ECM) were treated by different doses of ¹⁸⁸ Rhenium Perrhenate (¹⁸⁸ReO₄). To evaluate cell viability, live/dead assay carried out. The flow-cytometric assay, qRT-PCR, western bolting, colony formation assay, and immunofluorescence (IF) studies were performed to investigate the therapeutic effect of ¹⁸⁸ReO₄. Subsequently, the tumor formation ability of ¹⁸⁸ReO₄-treated Huh7 cells was evaluated in animal model.

Results

According to viability assay and live/dead staining, the number of dead cells in Huh7 and HepG2 lines were significantly increased compared to untreated control groups. Data obtained from Annexin/PI showed that Huh7 and HepG2 cells showed typical apoptotic changes after treatment with ¹⁸⁸ReO₄. Quantitative RT-PCR and western blotting data also supported that ¹⁸⁸ReO₄ treatment can induce apoptosis. Furthermore, cell cycle arrest observed in G2 phase after exposure to effective dose of ¹⁸⁸ReO₄ in Huh7 cells. Colony formation assay confirmed growth suppression in Huh7 and HepG2 cells post exposure. The IF also displayed proliferation inhibition in the ¹⁸⁸ReO₄ treated cells on 3D scaffolds of liver extracellular matrix (LEM). In 2D culture, PI3-AKT signaling pathway remained unchanged whereas, in the 3D condition it was activated. Treated Huh7 cells with effective dose of ¹⁸⁸ReO₄ lose their tumor formation ability in nude mice compare to the control group.

Conclusion

The results supported that ¹⁸⁸ReO₄ could induce apoptosis and cell cycle arrest and inhibit tumor formation capacity in HCC cells.

In this work, exchange radioiodination of metaiodobenzylguanidine (MIBG) was carried out at optimum conditions that facilitates the production of [¹³¹I]MIBG both quickly and efficiently. The radiochemical purity and yield of the labeled product are typically as high as 99% and 90% for diagnostic dose and 95% and 80% for therapeutic dose, respectively. Stability studies show that labeled material at the room temperature met the demand of the clinical application. This labeling procedure will be used in the routine production process of [¹³¹I]MIBG for diagnosis and treatment uses.

In this study the radioiodination process of meta-iodobenzylguanidine with ¹³¹I isotope in presence of ammonium sulphate and Cu(II) Catalyser was investigaded. In order to optimize the process, the influence of different parameters on labeling yield was studied. The results of experiments showed that the use of oil bath with temperature of 160˚C is necessary. After the labeling process, purification step of the final product was carried out using Dowex-1×8 resin. The mean labeling yield was 97.2%. In this method radiolabelling of MIBG with ¹³¹I (185 MBq for diagnostic dose and 3330 MBq for therapeutic dose) is quite simple and it complies with the requirements of routine production of ¹³¹I-MIBG radiopharmaceutical for diagnostic and therapeutic purposes. This paper is a narration of industrial scale production of ¹³¹I-MIBG radiopharmaceutical

Meta-iodobenzylguanidine (MIBG) is an analogue of the adergenic neuron blocking guanethidine. MIBG labeled with radioiodine is a very valuable radiopharmaceutical, where it is intensively used in nuclear medicine for both diagnostic imaging and targeted radiotherapy of neural crest derived
tumors, such as neuroblastoma and pheochromocytoma. We have developed in 2009 an in house method of labeling MIBG with 131I. Since then we are regularly preparing 131I-MIBG for scintigraphy, with a gradual increase in the number of preparations. Methods: The procedure involved the addition of 1 mg of MIBG, 4 mg of ammonium sulfate, 50 μl of glacial acetic acid and 20 μl of freshly prepared CuSO4, 5H2O (3.25 mg/ml), followed by 131I-sodium iodide (supplied by the Nuclear Science Research School of NSTRI, AEOI, Tehran, Iran) in a vial. All the reagents were pure. After sealing the vial, the mixture was heated at 160 ºC for 30 min in an oil bath. The final product was cooled and dissolved in 2 ml of 0.15 M sodium acetate solution prepared by using sterile N2-purged water for injection. The radiochemical yield and the purity were determined by thin layer chromatography. Stability of the produced [131I]MIBG was evaluated at different time intervals by checking the RC purity with paper chromatography. Results: In this work, we succeeded in direct radiolabeling of MIBG by means of isotopic exchange. It was found that the labelling efficiency could be affected by several factors such as the composition of the reaction mixture, the temperature and the period of reaction. The process produced high yields of radioiodination (>80%) with very high radiochemical purity (>98%) and high specific activity. The pH of the labelled product was between 5-6. The results of biodistribution as demonstrated in animal imaging studies, revealed  physiologic distribution of the radiopharmaceutical and images were similar to those of the commercial product. Conclusion: We have developed a method for 13lI-labeIled MIBG for routine-production process. This method has some acceptance because of the simplified set-up and fewer reagents required for the synthesis. The 131I-labelled MIBG has high radiochemical purity and the deiodination is low. The good images resulting from the use of locally prepared 131I-MIBG revealed a good quality.

Radiopharmaceuticals are now increasingly used for therapy of cancer, palliation of pain secondary to bone metastasis and for the treatment of rheumatoid arthritis.¹⁶⁵Ho (n, g) ¹⁶⁶Ho is currently used for radiotherapy due to its attractive properties which include emission of high energy b- particles (E_b-1=1855 Kev (51%), E_b-2=1776 Kev (48%) and E_ave=666 Kev), an appropriate physical half- life of 26.4 h and decay to stable daughter. In this research holmium oxide (Ho₂O₃, purity > 99.9%) was irradiated in Tehran research reactor (TRR) and four parameters mass, thermal neutron flux (j), bombarding time (tb) and cooling time (tc) were investigated. The best conditions for producing of ¹⁶⁶Ho were achieved (m=2 mg, j=5.7×10¹³ n/cm².s, t_b=8 h, t_c=40 h, correction factor 92%).