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Radiolabeled Antibody Fragment for Preparation of (177Lu-DOTA)m-PAMAM G3.0-F(ab’)2 trastuzumab as a Radiopharmaceutical for Cancer Therapy
Get PDFSeveral radiolabeled monoclonal antibodies (mAbs) have been used as radioimmunotherapy (RIT) agents for cancer therapy. The use of mAbs as RIT agents is due to their ability to carry effectors, in the form of radionuclides which emit alpha (α) particles, beta (β) particles, or auger electrons, and bind specifically to cancer expressed receptor. This paper reports the preparation of radiolabelled trastuzumab in form of (177Lu-DOTA)m-PAMAM G3-F(ab')2-trastuzumab, which will be expected as a potential RIT agent for therapy of breast cancer overexpressed human epidermal growth factor receptor 2 (HER2). Due to its reduced molecular weight, the use of F(ab')2-trastuzumab on the aforementioned RIT agent candidate is expected to reach its target much faster compared to the intact trastuzumab. Meanwhile, the role of PAMAM G3 is to increase the specific activity of the radiotherapeutic agent of Lu-177 due to the ability of its 32 –NH2 functional groups that are able to bind many DOTAs (£ 31) which in turn can bind a large number of 177Lu. The preparation was initiated by fragmentation of trastuzumab using pepsin enzyme in 0.02 M acetic acid buffer with a pH of 4.5 to produce F(ab')2-trastuzumab with a purity of 95 % after purification with PD-10 column. The F(ab')2-trastuzumab was then reacted with succinimidyl 4-(N-maleimidomethyl) cyclohexane-1-carboxylate (SMCC) to produce SMCC-F(ab')2-trastuzumab. The next reaction was to conjugate SMCC-F(ab')2-trastuzumab with DOTA-PAMAM G3.0-SH, which was prepared by reaction NHS-DOTA with PAMAM G3.0 and followed by reacting it with 2-iminothiolane to give (DOTA)m-PAMAM G3.0-F(ab')2-trastuzumab. Finally, the (DOTA)m-PAMAM G3.0-F(ab')2-trastuzumab was radiolabelled with 177Lu to produce (177Lu-DOTA)m-PAMAM G3.0-F(ab')2-trastuzumab, resulting in a radiochemical purity of 98 % after purification with PD-10 column.Received: 31 October 2015; Revised: 30 June 2016; Accepted: 25 September 201
The Evaluation of the Effective Diameter (Deff) Calculation and its Impact on the Size-Specific Dose Estimate (SSDE)
Get PDFInformation on the effective diameter (Deff) is essential for estimating the dose for patients undergoing CT examinations. The purpose of this study was to calculate the effective diameter using the maximum values of lateral (LAT) and anterior-posterior (AP) diameters (Deff,m) and using LAT and AP diameters taken from the center of the image (Deff,c), and compared both estimates to the effective diameter calculated directly from the cross-sectional area of the patient (Deff,A). We evaluated 164 patients who underwent the four most frequent CT examinations, namely pelvic, abdominal, thoracic, and head examinations, using a multi-detector CT (MDCT), the Toshiba Aquilion 128. We calculated the percentage differences between Deff,c and Deff,m from Deff,A. We also used the Wilcoxon-Mann-Witney U test to statistically determine whether differences were significant. While Deff,m is statistically no different (p 0.05) from Deff,A, Deff,c is statistically different (p ˂ 0.05) from Deff,A except for head examinations.Received: 31 May 2016; Revised: 14 December 2016; Accepted: 20 January 201
Field Performance of Five Soybean Mutants Under Drought Stress Conditions and Molecular Analysis Using SSR Markers
Get PDFThe objectives of this research wereto evaluate (1) the performance of soybean mutant lines under drought stress conditions, and(2) the genetic diversity and relationship among the mutant lines using SSR markers.The field evaluation was conducted during the dry season of 2011 and 2012 at the experimental Farm of Mataram University, West Nusa Tenggara, Indonesia. The field experiment was set up in a randomized block design. Ten mutant lines and two control varieties were evaluated in four replications. Genetic distance among evaluated lines were determined based on allelic diversity analysis using 40 simple sequence repeat (SSR) loci. Under drought stress conditions, two mutant lines, Kdl3 and Kdl8,showed a better performance compared to the other ones. The high yielding mutant lines were Kdl3and Kdl8, which yielded 1.75 t ha-1and 1.69 t ha-1, respectively, compared to the parent and national control, Panderman 1.43 t ha-1 and Muria 1.32 t ha-1. These mutant linesrequired 30.75 to 32days to flower and 79.75 to 83.75 day to harvest with relatively short plant height 28.25 and 23.35 cmrespectively. Those mutant characters were better than those of the other three mutants, the original parents, and the control soybean species. Since the evaluated soybean mutant lines yielded more under drought stress conditions than the standard varieties, they can be used and registered as drought-tolerant soybean mutants. Moreover, the evaluated soybean accessions showed a wide genetic distance. The accessions were clustered into two groups according to their genetic background, namelygroup I (the Panderman with three mutant lines) and group II (the Muria with two mutant lines). Twenty-three out of 40 evaluated SSR loci, including AW31, BE806, CMAC7L, S080, S126, S57, S171, S224, S285, S294, S393, S294, S383, S511, S511, S520, S540, S547, S551, S571, S577, and S578, provided polymorphic alleles between the parents and their mutants and could be used to differentiate mutants from their parents. Therefore, these loci are informative and may be useful for further analysis of soybean mutant lines in relation to breeding program
Comprehensive Prediction of Thermosyphon Characteristics in Reactor Passive Cooling System Simulation Loop FASSIP-01
Get PDFPassive cooling mechanism for a nuclear reactor has been proven to be very important since the Fukushima Daiichi Reactor accident that was caused by active cooling system malfunction due to total loss of electrical power source. In the Center for Nuclear Reactor Technology and Safety of BATAN, the cooling mechanism was studied by using a natural circulation test loop named FASSIP-01 that applied thermosyphon mechanism of water inside pipes of 1” diameter. This study aimed to analytically predictthe thermal characteristics of the loop including its response time towards steady condition usingthe MATLAB calculation program. This prediction derived the influence of several parameters such as the heat transfer coefficient of the cooler side (h-cooler), the heater power, the elevation difference between the heater and cooler(DZ), and the effects of the insulation thickness of pipe (IT) on the flowrate, temperature, and the heat power distribution across all components in the loop. The result showed that byavoiding boiling condition, for transferring the heater power of 1000 W and 2000 W,the needed h-cooler exceeds 200 and 400 W m-2°C-1, respectively. For a h-cooler of 200 W m-2°C-1, the circulation flow rate increased from 0.04 to 0.06 kg/s-1 for heater power increase from 1000 W to 2000 W. Those flow rates were decreased to 0.037 and 0.052 kgs-1 by increasing h-cooler to 1000 W m-2°C-1.The results were in agreement with other studies on rectangular loops in the literature.The time needed to reach 95 % towards steady state was predicted to be more than 13 hours. Reduction of this time to less than five hours was possible by reducing the heater tank volume from 100 L to 30 L or by modifying the starting heater input power
Profile of MIBI Liquid Phase Radiopharmaceutical for Myocardial Imaging
Get PDFThe 99mTc-MIBI radiopharmaceutical has been used innuclear medicine in Indonesia for myocardial imaging. BATAN researchers have mastered the technology to manufacture MIBI as a liophylized kit. A reformulation of MIBI radiopharmaceutical has been conducted to improve the stability of the kit especially in the liquid-phase kit. Basically, radiopharmaceuticals in liquid form are not different from the dry kit. However in the manufacturing of liquid-phase kit, lyophilization process was not done. To improve the stability of liquid kit, a reformulation of the components was conducted by using two separate vials (Formulation 2) and the characteristics were compared with the one-vial formulation (Formulation 1). The MIBI Formulation 2 consists of two vials, vial A containing 0.06 mg of SnCl2 2H2O and 2.6 mg Sodium Citrate 2H2O and vial B containing 0.5 mg of [Cu(MIBI)4]BF4, 1 mg of cysteine hydrochloride, and 20 mg of mannitol.The purposes of this study wereto determine the stability of two different formulations of MIBI as a liquid-phase kit, to compare their stability in different storage condition such as in refrigerator and freezer, and to compare the ratio of activities attained between target and nontarget organs after injection to animal model. As a diagnostic agent, MIBI was reconstituted with Technetium-99m as radionuclide tracer to 99mTc-MIBI labeled compound. The radiochemical purity of 99mTc-MIBI was determined by chromatography method using alumina thin-layer chromatography paper as the stationary phase and ethanol 95% as the mobile phase. The results showed MIBI Formulation 2 has a higher stability than Formulation 1. Formulation 2 also maintained a 96.68% radiochemical purity under 52-day storage and attained a target-to-nontarget activity ratio of 8.22.Received: 04 October 2014; Revised: 10 November 2015; Accepted: 25 November 201
The Investigation of 137Cs Contamination in Soils of Aceh after the Tsunami
Get PDFCs-137 is one of the most common radionuclides used for analysing man-made radioactive contamination in the environment beside Sr-90. Nangro Aceh Darussalam Province suffered the greatest mortality, with widespread destruction extending along more than 1000 km of coastline on 26 December 2004 due to tsunami. The disaster were affected areas about 220 km long and around 5 km wide along the coastlines of Aceh and North Sumatra. The purpose of this study is to investigate the artificial radioactivity 137Cs in soil samples which have been collected from various locations along the areas affected by tsunami in Aceh. The surface soil samples were collected from 20 sites in this region. The soil samples from the middle area of Aceh which was not exposed to the tsunami have also been investigated for comparison. The activity concentration of137Cs in the samples was measured using a ORTEC P-type coaxial high purity Germanium (HPGe) detector system. The artificial radioactivity level of 137Cs measured from these samples was found in the range of not detected to 2.09 Bq.kg-1 for the affected soil samples and 0.56 to 1.44 Bq.kg-1 for unaffected soil respectively. The radioactivity concentrations of 137Cs within the coastline areas are comparable to that of the middle area, which was not exposed to the tsunami. The results indicate that there are no new inputs of man-made radionuclides into the area at that time and the data obtained could serve as baseline levels of 137Cs in Aceh Region.Received: 29 May 2015 ; Revised: 02 November 2015; Accepted: 25 November 201
Simulations of Beam Quality in a 13 MeV PET Cyclotron
Get PDFSimulation of the trajectories of negative hydrogen ion (H−) beam in a 13 MeV PET cyclotron (DECY-13) were carried out by using the Runge-Kutta (RK4) approximation method and Scilab 5.4.1. The magnetic and electric fields were calculated using Opera-3d/TOSCA softwares at 1 mm resolution. The cyclotron is of a fourth-harmonics type, meaning that the acceleration occurs four times per cycle, with a radiofrequency (RF) field of 77.66 MHz frequency and 40 kV amplitude. The calculations and simulations show that the maximum distance between the ion source and the puller is about 6 mm, while the maximum width of the beam at 13 MeV is about 10 mm, and the initial phase between the RF field and the beam ranges from -10° to 10°, with a yield of about 10% of the beam from the ion source getting accelerated to 13 MeV.Received: 12 March 2015; Revised:30 June 2015; Accepted: 01 July 201