Indian Journal of Nuclear Medicine
Home | About IJNM | Search | Current Issue | Past Issues | Instructions | Ahead of Print | Online submissionLogin 
Indian Journal of Nuclear Medicine
  Editorial Board | Subscribe | Advertise | Contact
Users Online: 233 Print this page  Email this page Small font size Default font size Increase font size


 
 Table of Contents     
ORIGINAL ARTICLE
Year : 2013  |  Volume : 28  |  Issue : 2  |  Page : 70-74  

Indigenous technology development and standardization of the process for obtaining ready to use sterile sodium pertechnetate-Tc-99m solution from Geltech generator


Board of Radiation and Isotope Technology, Bhabha Atomic Research Centre, Navi Mumbai, Maharashtra, India

Date of Web Publication16-Sep-2013

Correspondence Address:
Arun Chandra Dey
Board of Radiation and Isotope Technology, Bhabha Atomic Research Centre, Navi Mumbai - 400 703, Maharashtra
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0972-3919.118226

Rights and Permissions
   Abstract 

Purpose of the Study: The indigenous design and technology development for processing large scale zirconium molybdate-Mo-99 (ZrMo-99) Geltech generator was successfully commissioned in Board of Radiation and Isotope Technology (BRIT), India, in 2006. The generator production facility comprises of four shielded plant facilities equipped with tongs and special process gadgets amenable for remote operations for radiochemical processing of ZrMo-99 gel. Results: Over 2800 Geltech generators have been processed and supplied to user hospitals during the period 2006-2013. Geltech generator supplied by BRIT was initially not sterile. Simple elution of Tc-99m is performed by a sterile evacuated vial with sterile and pyrogen free 0.9% NaCl solution to obtain sodium (Tc-99m) pertechnetate solution. A special type online 0.22 μm membrane filter has been identified and adapted in Geltech generator. Conclusions: The online filtration of Tc-99m from Geltech generator; thus, provided sterile Tc-99m sodium pertechnetate solution. Generators assembled with modified filter assembly were supplied to local hospital in Mumbai Radiation Medicine Centre (RMC) and S.G.S. Medical College and KEM Hospital) and excellent performances were reported by users.

Keywords: Geltech generator, hydromillex SLST025DM 0.22 μm sterile membrane filter, sterile sodium pertechnetate-Tc-99m, technology development


How to cite this article:
Sarkar SK, Kothalkar C, Naskar P, Joshi S, Saraswathy P, Dey AC, Vispute GL, Murhekar VV, Pilkhwal N. Indigenous technology development and standardization of the process for obtaining ready to use sterile sodium pertechnetate-Tc-99m solution from Geltech generator. Indian J Nucl Med 2013;28:70-4

How to cite this URL:
Sarkar SK, Kothalkar C, Naskar P, Joshi S, Saraswathy P, Dey AC, Vispute GL, Murhekar VV, Pilkhwal N. Indigenous technology development and standardization of the process for obtaining ready to use sterile sodium pertechnetate-Tc-99m solution from Geltech generator. Indian J Nucl Med [serial online] 2013 [cited 2019 Dec 8];28:70-4. Available from: http://www.ijnm.in/text.asp?2013/28/2/70/118226


   Introduction Top


There are several methods for routine separation of Tc-99m from molybdenum-99 (Mo-99) for use in hospital radiopharmacy. The alumina column based chromatography generator system for Tc-99m is the most used generator system world-wide. High specific activity Mo-99 (>10 3 Ci/g of Mo) obtained from fission of U-235 is adsorbed on an acidic alumina column and Tc-99m is eluted with normal saline, which is considered as the "gold standard" generator for Tc-99m. Due to simplicity of operation, column chromatographic generators are the method of choice. [1]

The essential requirement for alumina column chromatography generator is the high specific activity fission produced (n, f) Mo-99, which is expensive and not easily indigenously available in many developing countries. The reason for requirement of fission produced Mo-99 is that the acidic aluminum oxide has a limited adsorption capacity for molybdenum, 20 mg Mo/g of alumina, at pH, <4.5 and in turn dictates the column size and the final elution volumes and radioactive concentration of Tc-99m eluate. Because of this constraint, medium and low flux reactor produced (η, γ) Mo-99 (7.4-14.8 GBq {200-400 mCi} of Mo-99/g of Mo) easily accessible in developing countries cannot be used for alumina column chromatography generator. Production of 1 Ci Mo-99 by fission route produces about 100Ci of other gaseous and solid radioactive products, [2] which is a concern for the environment and costly waste management issue.

Although, it is possible to prepare generators with (η, γ) Mo-99, but generators made with such low specific activity Mo-99 require substantially larger columns which in turn, require increased volumes of eluent leading to low concentrations of Tc-99m and hence not suitable for radiopharmaceuticals formulations. An impressive number of studies have been reported for use of (η, γ) Mo-99 for separation of Tc-99m [3],[4],[5] for radiopharmaceutical use. Other alternative is to develop new adsorbent material for Mo of higher capacity for preparation of column generator using (η, γ) Mo-99. Japanese Scientists have reported success using an adsorbent, called polymeric zirconium compound (PZC). This is a new adsorbent material having higher adsorption capacity for Mo-99 (200 mg/g of PZC). Scientist in Bhabha Atomic Research Centre (BARC) has also reported about nano-zirconia, titania, and γ-alumina [6],[7],[8] adsorbent material for adsorption of molybdenum with higher adsorption capacities for preparing Mo-99/Tc-99m column generator.

Zirconium molybdate-Mo-99 (ZrMo-99) gel generator is a novel option, which combines both advantages of column generator and enables the utilization of indigenously produced low to medium specific activity (η, γ) Mo-99. The preparation of ZrMo-99 gel matrix involves several challenging radiochemical processing steps such as precipitation, filtration, drying, disintegration, washing and handling of ZrMo-99 gel powder. [9],[10],[11],[12],[13],[14],[15],[16],[17],[18],[19] The processing of large scale ZrMo-99 gel of reproducible quality is hence a challenging task for remote operation and automation, which have been overcome in Board of Radiation and Isotope Technology (BRIT). [12],[13],[14],[15],[16] The indigenous facility has four shielded plant (with 100 mm lead shielding) connected in series comprising of remotely operated gadgets for transferring sodium molybdate (Mo-99) solution for precipitation with ZrOCl 2·8H 2 O solution in a reaction vessel, filtration of ZrMo-99 gel precipitate using specially fabricated Buchner funnel under vacuum, transferring and discharge of gel precipitate to a pneumatic-driven ZrMo-99 collection dish, keeping the dish in a microwave oven for drying gel, specially designed dispenser for dispensing particular volume of dry gel powder in glass column stationed in an indexer table, sealing of gel column and loading of gel columns into the pre-assembled generator housing etc. The indigenous facility for regular processing of Geltech generator has been successfully commissioned in BRIT, India in 2006 [18] and successfully used until mid-2012.

Conversion of 50 g of Mo into 170-180 g ZrMo-99 gel powder in two cycles of 25 g/batch is found feasible in the present facility. [20] Market studies revealed that generators of activity minimum of 400-500 mCi (15-18.5) GBq Mo-99 on Monday would be required by most hospitals. The specific activity of indigenously produced (η, γ) Mo-99 was in the range of 7.4-14.8 GBq/g of Mo, there was a need to spike with (n, f) Mo-99 for preparing clinically useful generators of 15 GBq Mo-99 generator on Monday. In case of non-availability of (n, f) Mo-99, gel generators of 250 mCi (9.25 GBq) Mo-99 on Monday were prepared using (η, γ) Mo-99 alone containing larger quantity gel 9-10 g bed (3-4g Mo) to sustain regular supply of generator. The pH adjustment of gel and drying of gel cake are the most important for processing so as to get gel of desired quality. Depending upon the pH, both transitional metals form multiple polymeric species in aqueous solutions and produce quantitative precipitate of ZrMo-99 gel and subsequent drying give amorphous gel powder with varying water molecules, which facilitates free diffusion of Tc-99m from gel generator during elution. Performance evaluation of gel generators were carried out in terms of elution of Tc-99m, which were smooth, rapid and completed in about 2 min. Clear eluates of pH 5-6 were always observed. The consistent results of over 75% yield of Tc-99m, <10−2 % Mo-99 breakthrough, >95% Radiochemical Purity (RC) purity of pertechnetate, less than 10 ppm of Mo, Zr and Al in eluates could achieved. Compatibility of this Tc-99m for formulating even sensitive Tc-99m compounds such as Tc-L, L-ethyl cysteinate dimer, and Tc-methoxy isobutyl isonitrile indicated satisfactory quality of pertechnetate (Tc-99m). Good quality images were reported by various users.

Geltech generators of capacity 250-400 mCi (9.25-14.8 GBq) Tc-99m are being processed regularly and supplied by BRIT on a weekly basis to the different nuclear medicine centers across India. [19],[20] It is a dual column system comprising of primary gel column and a secondary purification alumina column connected in tandem. Elution of Tc-99m is carried out by the users by passing 10 ml normal saline through the gel column and collecting Tc-99m in a sterile evacuated vial connected at the end of a secondary alumina column. The users were advised to sterile Tc-99m sodium pertechnetate eluted in 0.9% NaCl solution either by autoclaving at 121°C for 30 min at 15 psi or using 0.22 μm membrane filtration for labeling before patient administration. Many other commercial suppliers for Tc-99m alumina column chromatography generators such as Isorad, Amersham, CIS-Bio etc. are supplying generators with on-line 0.22 μm membrane filters for providing sterile sodium Tc-99m pertechnetate. Therefore, there was a definite need to avoid the extra step of sterilization of Tc-99m from gel generator. Our aim of the studies were to supply column type Geltech generator with modified generator assembly, so as to accommodate an on-line 0.22 μm membrane filter, for providing sterile sodium (Tc-99m) pertechnetate throughout the shelf-life of the generator for the users. [20] The specialty of the membrane is that it is composed of both hydrophilic and hydrophobic membrane housed in the same filter assembly permitting repeated passage of sterile saline and sterile air. Thus, a single filter can be used unchanged throughout the generator shelf-life. Large numbers of Tc-99m eluates (more than 100) were collected using this filter from 8 batches of Geltech generators. Sterility and pyrogenicity of sodium (Tc-99m) pertechnetate solution was found to meet with Indian pharmacopoeial (IP) requirement. The Geltech generator system with modified filtration assembly has been adopted in the present Geltech generator system, which can be used in due course in hospital radiopharmacy for obtaining sterile and apyrogenic sodium (Tc-99m) pertechnetate solution.

A total of 238 batches of Geltech generators have been processed (with a maximum of 24 generators per batch, containing up to 44 GBq (1.2 Ci) Mo-99 (on production day) in 5-6 g and sometimes 9-10 g ZrMo-99 gel powder and supplied to user hospitals including 14 field trial batches.

We report our results on processing of a large number of Geltech generator and sterility and apyrogenicity of sodium (Tc-99m) pertechnetate obtained from Geltech generator in this paper.


   Materials and Methods Top


All chemicals used were from commercial sources and mostly of GR/AR grade. Aluminum oxide active acidic, 100-200 mesh, of Brockman grade 1, for chromatographic analysis, from Prabhat Chemicals, Mumbai was used. (η, γ) Mo-99 was available as sodium molybdate in 3.5 M NaOH (150 mg of Mo/ml, concentration: 1.1-2.2 GBq/ml, specific activity: 7.4-15 GBq/g of Mo) from Radiochemical Section, Radiopharmaceuticals Division, BARC. The different types of glass columns, needles, rubber stopper used were procured locally. Filter sterile hydromillex (hydrophilic and hydrophobic filter) pore size 0.22 ηm, sterile, 25 mm dia, separately packed filter, Millipore Cat.: No. SLST025DM was procured from Pramukh Healthcare, Mumbai. Polypropylene barbed Luer adapter male luer with lock connector was procured from Cole Parmer. Kits for Tc-99m compounds were in-house produced. An ionization chamber (NPL, UK) pre-calibrated with Cs-137 and Atomlab dose calibrator were used for the assay of radioactivity.

Modification of the gel generator for assembling of on-line 0.22 μm membrane filter

In order to adopt an on-line 0.22 μm membrane filter the modification of Geltech generator has done in the following way. The ZrMo-99 gel column and the secondary purification alumina column are connected with a stainless steel U-needle. There are two needle adopters, one for 10 ml saline charge and another for collecting Tc-99m O4 in the 15 ml evacuated vial. The elution of the Tc-99m requires around 1-2 min through both the columns. A stainless steel adapter has been made to accommodate on-line 0.22 μm membrane filters with connecter at the alumina column end for collection of Tc-99m through the on-line 0.22 μm membrane filter.

[Figure 1] shows the photograph of the Geltech generator with on-line 0.22 μm membrane filters.
Figure 1: Gel generator with sterile filter assembly

Click here to view


Evaluation of performance of Tc-99m gel generator

The general procedure for preparing ZrMo-99 gel generators and their performance evaluation has been described earlier. [12],[13],[14],[15],[16],[17],[18] (η, γ) Mo-99 was converted into insoluble ZrMo-99 with mole ratio of reactant Mo: Zr was 1:1.25 and pH of the precipitate was adjusted to 4-5 with 4 N NaOH. The dried gel was disintegrated with normal saline, re-dried using IR lamp under suction to obtain free flowing gel granules. ZrMo-99 gel powder then transferred to a glass column (35 mm × 13 mm). The gel column containing 6-7 g (~2 g Mo) ZrMo-99 granules was sealed and assembled in the generator assembly.

The Geltech generator performance in terms smoothness of elution, pH and clarity of eluate, Tc-99m elution yield and Mo-99 breakthrough were ascertained. The quality of pertechnetate eluate was evaluated as per the IP specifications. The pharmaceutical purity aspects, sterility and apyrogenicity were checked by carrying out conventional sterility and apyrogenicity tests on decayed Tc-99m eluates. [21],[22] Sterility and pyrogen tests performed for 5 generators and 27 Tc-99m eluates selected randomly from different batches of geltech generator.


   Results and Discussion Top


Geltech generator of capacity 250-400 mCi (9.25-14.8 GBq) Mo-99 activity are prepared and supplied to hospitals. The production data of Geltech generator since 2006 (April-March) is shown in [Table 1] and the indigenous production facility is shown in [Figure 2]. Normal elution of Tc-99m from Geltech generator is performed by passing 10 ml of 0.9% normal saline through the primary ZrMo-99 gel column and collecting in a 15 ml sterile evacuated vial connecting at the Tc-99m collection end after secondary alumina column. Sterility of Tc-99m eluates is performed either by using sterile 0.22 μm membrane filter or autoclaving Tc-99m eluates. In the case of using the sterile 0.22 μm membrane hydrophilic filter (meant for single use) of Tc-99m eluates, there could be a loss of Tc-99m activity (~10%) due to the hold-up of Tc-99m solution in the filter medium. The same filter can't be used for subsequent filtration due to the formation of impervious air-film on the membrane filter. Whereas, in the case sterility obtained by autoclaving the product at 121°C for 30 min at 15 psi, there could be a loss of Tc-99m activity (10-11%) due to decay loss (it may take ~45-60 min for heating and then cooling of the product for use and 0.89% is the decay factor for Tc-99m for an hour).
Figure 2: Tc-99m Geltech generator production facility

Click here to view
Table 1: The production data of Geltech generator since 2006 (April-March)


Click here to view


The loss of Tc-99m activity due to decay and hold-up of activity in the membrane have been avoided by using on-line sterile 0.22 μm hydromillex membrane filter where both the hydrophilic and hydrophobic membrane filter are housed in the same polypropylene housing. The filter connected on-line can be used unchanged without affecting the quality of pertechnetate-Tc-99m and performance of the generator. Geltech generators which are evaluated under this investigation have modified generator assembly with on-line sterile 0.22 μm membrane filter. The elution efficiency for Tc-99m (average ~83%), Mo-99 break through (radionuclidic purity) and other quality features of eluted Tc-99m are summarized in [Table 2]. Colorimetric spot tests for Zr, Al, Mo were carried out as limit tests, which were less than 10 ppm. The radiochemical purity of Tc-99m O4 was >99% while that of the labeled formulation prepared using pertechnetate was >95%. Typical performance evaluation of Geltech generator for a period of 14 days with on-line 0.22 μm membrane filters is shown in [Table 3].
Table 2: Performance evaluation of Geltech generators with online 0.22 ìm membrane filter


Click here to view
Table 3: Typical performance evaluation of Geltech generator with online 0.22 ìm membrane filter


Click here to view


There is almost negligible loss of volume of Tc-99m eluates in the elution process with sterile 0.22 μm membrane filter. The pH of all the eluates was in the range of 4.5-6. Sterility test results of 15 Geltech generators show the eluates are sterile and apyrogenic which is shown in [Table 4]. The sterility of Tc-99m eluates selected randomly were tested from eight different batches of geltech generators for a period of 10- 21 days and found to meet IP requirement and shown in [Table 5]. The eluates of Geltech generators, which were evaluated post-expiry also showed that the eluates were also apyrogenic [Table 6].
Table 4: Sterility and pyrogen test data of sodium (Tc-99m) pertechnetate eluates from Geltech generator with 0.22 m m on-line membrane filter


Click here to view
Table 5: Sterility test results of Tc-99m eluates from Geltech generator with on-line 0.22 m m membrane filter


Click here to view
Table 6: Pyrogen test results of Tc-99m eluates from Geltech generator with on-line 0.22 m m membrane filter


Click here to view



   Conclusion Top


We have thus adopted a simple procedure for obtaining ready to use sterile and apyrogenic sodium (Tc-99m) pertechnetate from Geltech generator.


   Acknowledgments Top


The constant support received from Dr. A. K. Kohli, Chief Executive, Board of Radiation and Isotope Technology (BRIT), for the work is acknowledged. The authors are grateful to Dr. Meera V, Director, Division of Physical and Chemical Sciences, International Atomic Energy Agency (IAEA), A-1400, Vienna, Austria for her guidance and support for this work. The authors also acknowledge Dr. N. Ramamoorthy, Sr. Technical Advisor to Chairman, Atomic Energy Commission (AEC) and Associate Director (international collaboration and technical co-ordination), Ex-Director, Physical and Chemical Science Division, IAEA, Vienna for his keen interest, support and guidance for setting up the production facility of Geltech generator. The authors are also thankful to the collaborating hospital for these studies.

 
   References Top

1.Boyd RE. Technetium-99m generators - The available options. Int J Appl Radiat Isot 1982;33:801-9.  Back to cited text no. 1
[PUBMED]    
2.Vertes A, Nagy S, Klencsar Z. Handbook of Nuclear Chemistry, Radiochemistry and Radiopharmaceutical Chemistry in Life Sciences. Vol. 4. Dordrecht: Kluwer Academic Publishers; 2003.  Back to cited text no. 2
    
3.Chattopadhyay S, Das SS, Barua L. A simple and rapid technique for recovery of 99mTc from low specific activity (n,gamma)99Mo based on solid-liquid extraction and column chromatography methodologies. Nucl Med Biol 2010;37:17-20.  Back to cited text no. 3
[PUBMED]    
4.Chattopadhyay S, Das SS, Barua L. A simple and rapid technique for recovery of (99m)Tc from low specific activity (n,gamma)(99)Mo based on solvent extraction and column chromatography. Appl Radiat Isot 2010;68:1-4.  Back to cited text no. 4
[PUBMED]    
5.Chattopadhyay S, Barua L, De A, Saha Das S, Kuniyil R, Bhaskar P, et al. A computerized compact module for separation of (99m)Tc-radionuclide from molybdenum. Appl Radiat Isot 2012;70:2631-7.  Back to cited text no. 5
[PUBMED]    
6.Chakravarty R, Shukla R, Gandhi S, Ram R, Dash A, Venkatesh M, et al. Polymer embedded nanocrystalline titania sorbent for 99Mo-99mTc generator. J Nanosci Nanotechnol 2008;8:4447-52.  Back to cited text no. 6
[PUBMED]    
7.Chakravarty R, Shukla R, Ram R, Tyagi AK, Dash A, Venkatesh M. Practicality of tetragonal nano-zirconia as a prospective sorbent in the preparation of 99Mo/99mTc generator for biomedical application. Chromatographia 2010;72:875-84.  Back to cited text no. 7
    
8.Chakravarty R, Ram R, Dash A, Pillai MR. Preparation of clinical-scale 99Mo/99mTc column generator using neutron activated low specific activity 99Mo and nanocrystalline γ-Al 2 O 3 as column matrix. Nucl Med Biol 2012;39:916-22.  Back to cited text no. 8
[PUBMED]    
9.Boyd RE. The gel generator option: A viable alternative source of 99mTc for nuclear medicine. Appl Radiat Isot 1997;48:1027-33.  Back to cited text no. 9
    
10.Evans JV, Moore PW, Shying ME, Sodeau JM. Zirconium molybdate gel as a generator for technetium-99m - I. The concept and its evaluation. Int J Rad Appl Instrum A 1987;38:19-23.  Back to cited text no. 10
[PUBMED]    
11.Moore PW, Shying ME, Sodeau JM, Evans JV, Maddalena DJ, Farrington KH. Zirconium molybdate gel as a generator for technetium-99m - II. High activity generators. Int J Rad Appl Instrum A 1987;38:25-9.  Back to cited text no. 11
[PUBMED]    
12.Saraswathy P, Sarkar SK, Patel RR, Arora SS, Narasimhan DV. 99mTc Gel generators based on zirconium molybdate-99Mo: I: Process standardization for production. Radiochim Acta 1998;83:97-02.  Back to cited text no. 12
    
13.Saraswathy P, Sarkar SK, Patel RR, Arora SS, Narasimhan DVS. 99mTc Gel generators based on zirconium molybdate-99Mo: II: Evaluation of preparation and performance. Radiochim Acta 1998;83:103-7.  Back to cited text no. 13
    
14.Saraswathy P, Sarkar SK, Narasimhan DV, Patel RR, Ramamoorthy N. Microwave oven drying of zirconium molybdate-99Mo for use in 99mTc Gel generator. Appl Radiat Isot 1999;50:277-81.  Back to cited text no. 14
    
15.Sarkar SK, Saraswathy P, Arjun G, Ramamoorthy N. High radioactive concentration of 99mTc from a zirconium 99Mo molybdate gel generator using an acidic alumina column for purification and concentration. Nucl Med Commun 2004;25:609-14.  Back to cited text no. 15
[PUBMED]    
16.Saraswathy P, Sarkar SK, Arjun G, Nandy SK, Ramamoorthy N. 99mTc gel generators based on zirconium molybdate-99Mo: III: Influence of preparatory conditions of zirconium molybdate-99Mo gel on generator performance. Radiochim Acta 2004;92:59-64.  Back to cited text no. 16
    
17.Sarkar SK, Kothalkar C, Naskar P, Arjun G, Saraswathy P, Dey AC, et al. Experience with the preparation of 99Mo-99mTc gel generator and supply to Hospitals. Indian J Nucl Med 2006;21:79.  Back to cited text no. 17
    
18.Saraswathy P. Chemical process related technology development for production of zirconium molybdate-Mo99 based 99mTc gel generators: Indian experience. In: Proceedings of DAE/BRNS Symp. on Nucl. & Radiochem, NUCAR 2007. p. 45-8.  Back to cited text no. 18
    
19.Sarkar SK, Kothalkar C, Naskar P, Saraswathy P, Dey AC, Kohli AK, et al. Update on operational experience of zirconium molybdate-99Mo gel generator production in India. In: RERTR-2009 - 31 st International Meeting on Reduced Enrichment for Research and Test Reactors, Beijing, China, Nov 1-5 th , 2009. Available from: http://www.rertr.anl.gov/RERTR, 2009.  Back to cited text no. 19
    
20.Sarkar SK, Kothalkar C, Naskar P, Vispute GL, Joshi S, Saraswathy P, et al. Sterile sodium pertechnetate-99mTc from Geltech generator. Indian J Nucl Med 2010;25:124.  Back to cited text no. 20
    
21.Indian Pharmacopoeia. Pyrogens 2010;2.2.8:36.  Back to cited text no. 21
    
22.Indian Pharmacopoeia. Sterility 2010;2.2.11:56.  Back to cited text no. 22
    


    Figures

  [Figure 1], [Figure 2]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]



 

Top
  
 
  Search
 
  
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

 
  In this article
    Abstract
   Introduction
    Materials and Me...
    Results and Disc...
   Conclusion
   Acknowledgments
    References
    Article Figures
    Article Tables

 Article Access Statistics
    Viewed1674    
    Printed37    
    Emailed0    
    PDF Downloaded112    
    Comments [Add]    

Recommend this journal