Development of 99Mo/99mTc Generator System for Production of Medical Radionuclide 99mTc using a Neutron-activated 99Mo and Zirconium Based Material (ZBM) as its Adsorbent

Molybdenum produced from fission of U-235 is the most desirable precursor for 99Mo/99mTc generator system as it is non-carrier added and has high specific activity. However, in the last decade there has been short supply of 99Mo due to several constrains. Therefore, there have been many works performed for development of 99Mo/99mTc generator system using 99Mo which is not produced from either LEU or HEU. This report deals with development of 99Mo/99mTc generator system where zirconium-based material (ZBM) is used as adsorbent of neutron-activated 99Mo. The system was prepared by firstly irradiating natural Mo in the G. A. Siwabessy reactor to produce neutron-activated 99Mo. The target was dissolved in NaOH 4N and then neutralized with 12 M HCl. The 99Mo solution was then mixed with a certain amount of ZBM followed by heating at 90°C for three hours to allow the 99Mo adsorbed on ZBM. The 99Mo-ZBM (9.36 GBq of 99Mo was Mo/ 4.2 g ZBM) was packed on a fritz-glass column. This column was then fitted serially with an alumina column for trapping 99Mo breakthrough. The columns were then eluted daily with saline solution for up to one week. The yield of 99mTc was found to be between 53.7 – 74% (n= 5). All 99mTc eluates were clear solutions with pH of 5. Breakthrough of 99Mo in 99mTc eluates was found to be 0.031 ± 0.019 μCi 99Mo/ mCi 99mTc (n= 5) which was less than the maximum activity of 99Mo allowed in 99mTc solution (< 1 µCi 99Mo/mCi 99mTc). Aluminum breakthrough in 99mTc eluates was found to be less than 10 ppm. The radiochemical purity of 99mTc in form of Na99mTcO4 was > 99%. Radiolabeling of this 99mTc towards methylene diphosphonate (MDP) kit gave a radiolabelling efficiency of 99%. In summary, a new 99Mo/99mTc generator system that used neutron-activated 99Mo and ZBM as its adsorbent has been successfully prepared. The 99mTc produced from this new 99Mo/99mTc generator system attained the quality of 99mTc required for medical purposes.Received: 23 Februari 2016; Revised: 13 July 2016; Accepted: 17 July 201

Radiolabeling Technique of Silver Nanoparticles (AgNPs) with Iodine-131 Radionuclide

 Radiotherapy is an effective cancer therapy, where a certain dose of radiation is aimed specifically at target and is unaffecting to normal tissue. A selectiveradionuclide must be attached to the specific targeted organ. In this research, silver nanoparticles (AgNPs) were labeled with radionuclide of iodine-131 (131I) to be used in radiotherapy. Silver nanoparticles were synthesized using silver nitrate 0.0005 M, sodium borohydride 0.002 M, polyvinylpyrrolidone 0.3 % (w/v) and natrium chloride 1.5 M, and then followed by purification by centrifugation. Characterization was carried out with UV-Vis spectrophotometer, transmission electron microscope, particle size analyzer, and zeta-sizer. The results show that the maximum absorbance is on a wavelength of 398 nm, spherical shape with a diameter of 10 nm, polydispersity index of 0.455, and zeta potential value of –8 mV. The radiolabeling was done by adding sodium iodide-131 which had been oxidized by chloramine-T and immobilized in AgNPs colloidal solution, and the activity was then measured using a dose calibrator. The identification of radionuclide showed that the sample was free of impurities. The optimum system of radiochemical purity was obtained using Whatman 1 paper strip as the stationary phase and a mixture of methanol: water: ammonium acetate (1:1:1) as the mobile phase, which gave 96 % purity. This method is suitable for radiolabeling AgNPs with 131I to be used for radiotherapy

Separation of Radiocopper 64/67Cu from the Matrix of Neutron-Irradiated Natural Zinc Applicable for 64Cu Production

Radioisotope 64Cu is a promising radiometallic-isotope for molecular-targeted-radiopharmaceuticals. Having a half-life of 12.70 hours and emitting β+-radiation (Eβ+ = 0.6531 MeV) as well as β-ray (Eβ- = 0.5787 MeV), it is widely used in the form of biomedical-substrate-radiopharmaceutical for positron emission tomography (PET) diagnosis and simultaneously for targeted radiotherapy of cancer. The potential needs on the availability of 64Cu-labeled pharmaceuticals for domestic nuclear medicine hospitals lead to a necessity for the local production of carrier-free 64Cu using BATAN’s G.A. Siwabessy reactor because of the technical and economical constraints in the production using BATAN’s cyclotron. The presented work is accordingly to study whether the radioisotope 64Cu can be produced and separated from the matrix of post-neutron-irradiated-natural zinc. This study is expected can be further improved and implemented in production technology of carrier-free 64Cu based on 64Zn (n,p) 64Cu nuclear reaction exploiting the fast neutron fraction among the major thermal fraction due to unavailability of fast-neutron-irradiation facility in the BATAN’s G.A. Siwabessy reactor. The solution of post-neutron-irradiated-natural zinc in 1M acetic acid was loaded into Chelex-100 cation exchanger resin column to pass out the Zn/Zn* fraction whereas the Cu* fraction which remained in the column was then eluted out from the column by using 1.5 M HCl and loaded into the second column containing Dowex-1X8 anion exchanger resin. The second column was then eluted with 0.5 M HCl. The collected eluate was expected to be zinc-free Cu* fraction. It was observed from the half-life and the γ-spectrometric analysis that radioactive copper-64Cu containing 67Cu was produced by neutron activation on the natural Zn-foil target and can be separated from the target matrix by the presented two-steps-column-chromatographic separation technique. The radioactivity measurement showed that wrapping the Zn target with cadmium foil increased the activity of radioactive copper and, thus, the Cu*/Zn*-ratio.Received: 28 June 2011; Revised: 21 February 2012; Accepted: 24 February 201

Pengaruh Aktivitas 99mo Terhadap Profil Rendemen 99mtc Pada Generator 99mo/99mtc Dengan Kolom Material Berbasis Zirkonium (Mbz)

Pusat Teknologi Radioisotop dan Radiofarmaka (PTRR) BATAN telah mengembangkan Material Berbasis Zirkonium (MBZ) dengan kapasitas serap terhadap Molibdenum-99 (99Mo) lebih dari 150 mg Molibdenum/gram. Material ini masih perlu dikembangkan, salah satunya adalah kemampuannya untuk melepaskan Teknesium-99m (99mTc) pada saat proses elusi. Pada penelitian ini, dilakukan studi pengaruh aktivitas 99Mo terhadap profil rendemen 99mTc. Variasi aktivitas 99Mo yakni diserapkan ke dalam MBZ, kemudian 99mTc dielusi setiap hari sampai hari keenam dengan menggunakan larutan NaCl 0,9%. Berdasarkan analisis ANOVA two-factor without replication dengan taraf signifikansi 5%, ditemukan adanya perbedaan yang signifikan pada profil rendemen 99mTc dengan variasi aktivitas 99Mo (P-value=0,017631), perbedaan juga ditemukan pada pola garis regresinya. Semakin besar aktivitas 99Mo yang diserapkan ke MBZ, semakin rendah persentase hasil elusi 99mTc yang diperoleh pada hari pertama dan cenderung meningkat pada elusi berikutnya

Preparation and Characterization of Zirconia Nanomaterial as a Molybdenum-99 Adsorbent

The present study deals with the synthesis and characterization of ZrO2 nanomaterial which can be used as an adsorbent for Molybdenum-99 (99Mo). The adsorbent can potentially be utilized as the material for 99Mo/99mTc generator column. Using the sol-gel method, monoclinic nanocrystalline zirconia was synthesized from zirconium oxychloride in isopropyl alcohol reacted with ammonium hydroxide solution in isopropyl alcohol resulting in a white gel. The gel was subsequently refluxed for 12 hours at ~95°C and pH at ~4 and then dried at 100°C. The drying gel was then calcined at 600°C for two hours. Meanwhile the orthorhombic nanocrystalline zirconia was obtained by reacting zirconium oxychloride solution with 2.5 M ammonium hydroxide solution which resulted in a white gel. The gel was then refluxed for 24 hours at ~95°C and pH at ~11 and then dried at 100°C. The drying gel was then calcined at 600°C for two hours. These materials were characterized using FT-IR spectroscopy, X-ray diffraction (XRD), and Transmission Electron Microscope (TEM). The Scherrer method is used for determination of crystallite size. The FT-IR spectra for both materials show absorption peak at 450-500 cm-1 which are attributed to Zr-O bond. The XRD pattern of monoclinic nanocrystalline form shows crystalline peaks at 2θ regions of 28.37°, 31.65°, 34°, 36°, and 50.3° with average crystallite size of 2.68 nm. Meanwhile, the XRD pattern of orthorhombic nanocrystalline form shows crystalline peaks at 2θ regions of 30°, 35°, 50°, and 60° with average crystallite size of 0.98 nm. The TEM micrograph indicates that the zirconia nanomaterials prepared were quite uniform in size and shape.Received: 12 November 2015; Revised: 9 September 2016; Accepted: 20 September 201

Preparation and Characterization of Zirconia Nanomaterial as a Molybdenum-99 Adsorbent

The present study deals with the synthesis and characterization of ZrO2 nanomaterial which can be used as an adsorbent for Molybdenum-99 (99Mo). The adsorbent can potentially be utilized as the material for 99Mo/99mTc generator column. Using the sol-gel method, monoclinic nanocrystalline zirconia was synthesized from zirconium oxychloride in isopropyl alcohol reacted with ammonium hydroxide solution in isopropyl alcohol resulting in a white gel. The gel was subsequently refluxed for 12 hours at ~95°C and pH at ~4 and then dried at 100°C. The drying gel was then calcined at 600°C for two hours. Meanwhile the orthorhombic nanocrystalline zirconia was obtained by reacting zirconium oxychloride solution with 2.5 M ammonium hydroxide solution which resulted in a white gel. The gel was then refluxed for 24 hours at ~95°C and pH at ~11 and then dried at 100°C. The drying gel was then calcined at 600°C for two hours. These materials were characterized using FT-IR spectroscopy, X-ray diffraction (XRD), and Transmission Electron Microscope (TEM). The Scherrer method is used for determination of crystallite size. The FT-IR spectra for both materials show absorption peak at 450-500 cm-1 which are attributed to Zr-O bond. The XRD pattern of monoclinic nanocrystalline form shows crystalline peaks at 2θ regions of 28.37°, 31.65°, 34°, 36°, and 50.3° with average crystallite size of 2.68 nm. Meanwhile, the XRD pattern of orthorhombic nanocrystalline form shows crystalline peaks at 2θ regions of 30°, 35°, 50°, and 60° with average crystallite size of 0.98 nm. The TEM micrograph indicates that the zirconia nanomaterials prepared were quite uniform in size and shape.Received: 12 November 2015; Revised: 9 September 2016; Accepted: 20 September 201

Karakteristik Pemisahan Radiolutesium-177/177mlu dan Radioiterbium-169/175yb pada Kolom Resin Ln-eichrom

KARAKTERISTIK PEMISAHAN RADIOLUTESIUM- 177/177mLu DAN RADIOITERBIUM-169/175Yb PADA KOLOM RESIN LN-EICHROM. Radiolutesium-177Lu keradioaktifan jenis tinggi merupakan salah satu radiolantanida yang banyak digunakan untuk menangani berbagai kasus kanker, namun di Indonesia penggunaan radiofarmaka bertanda 177Lu belum dapat dijanjikan karena teknik produksi radioisotop primernya belum dikuasai. Prospek produksi 177Lu melalui reaksi inti 176Yb (n,g) 177Yb* à 177Lu* + β– dipelajari melalui metode pemisahan matrik 177/177mLu-169/175Yb/176Yb dalam sistem kromatografi kolom resin LN-Eichrom. Profil fraksinasi dan karakteristik pemisahan dipelajari dengan pemeriksaan keradioaktifan dan analisis spektro-metri-g terhadap hasil elusi larutan sasaran pasca iradiasi. Bahan sasaran digunakan 176Yb2O3 alam dan 176Lu2O3 diperkaya. Hasil penelitian menunjukkan bahwa radiolutesium-177/177mLu dapat dipisahkan dari matrik radioiterbium-169/175Yb/natYb melalui sistem kromatografi kolom dengan fase diam resin LN-Eichrom dan fase gerak larutan HNO3, dengan konsentrasi antara 1,5 – 4 M untuk mendapatkan pemisahan yang efektif, selektif dan kuantitatif. Reaksi inti 176Yb(n,g) 177Yb* à 177Lu + β– merupakan model reaksi inti yang perlu dipertimbangkan walau-pun harus melibatkan tahapan pemisahan produk 177Lu dari matrik sasaran Yb pasca iradiasi. Prosedur pemisahan yang dilakukan masih perlu diperbaiki melalui pemilihan jenis dan konsentrasi fase gerak pengelusi yang lebih tepat

Sintesis Poli N-Isopropilakrilamida (PNIPA)/Polityrosin (PTYR) Interpenetrating Polymer Networks (IPNs) Bertanda Iodium-125

Saat ini perkembangan polimer telah semakin maju, berbagai aplikasi polimer telah dikembangkan baik di sektor energi, pangan maupun kesehatan. PNIPA/PTYR IPNs bertanda iodium-125 dapat dimanfaatkan sebagai sumber terapi kanker. PNIPA/PTYR merupakan polimer peka temperatur. Tujuan dari penelitian ini adalah sintesis PNIPA/PTYR IPNs bertanda iodium-125. Polityrosin ditandai dengan iodium-125 kemudian secara simultan direaksikan dengan monomer N-isopropilakrilamida melalui polimerisasi radikal bebas dengan inisiator amonium persulfat (APS) dan tetrametiletilenediamin (TEMED) untuk memperoleh PNIPA/PTYR IPNs bertanda iodium-125. Kemurnian radiokimia PNIPA/PTYR IPNs bertanda iodium-125 diukur dengan krom atografi lapis tipis (KLT) dengan fasa gerak 2 propanol: 1 butanol: 0,2 M NH4OH. Selain Itu, stabilitas PNIPA/PTYR IPNs bertanda iodium-125 diuji pada media air. PNIPA/PTYR IPNs telah berhasil ditandai dengan iodium-125 dengan rendemen penandaan sebesar 37,6 ± 4,2 % (n = 3). Hasil pengamatan visual, ditunjukkan bahwa polimer mengalami Perubahan sifat pada temperatur 32 oC sampai dengan 34°C. Hasil H-NMR hanya menunjukkan spektrum dari polimer PNIPA. Berdasarkan pemeriksaan KLT, kemurnian radiokimia PNIPA/PTYR IPNs bertanda iodium-125 adalah 95,93%. Pengujian stabilitas polimer bertanda iodum-125 pada media air pada T = 37°C selama 2 minggu menunjukkan bahwa iodium-125 yang masih tertahan pada polimer adalah 71,3 ± 6,2 %

The Use of Sodium Hypochlorite Solution for (n,γ)99Mo/99mTc Generator Based on Zirconium-Based Material (ZBM)

The many problems in preparing fission product 99Mo led into this work to develop 99Mo/99mTc generator using neutron-irradiated natural MoO3 targets and, more specifically, to develop a zirconium-based material (ZBM) for chromatography columns that have an adsorption capacity of more than 100 mg Mo/g ZBM. This paper reports our recent experiments in the use of sodium hypochlorite solution of various concentrations to improve the yield of 99mTc in performance of (n,γ)99Mo/99mTc generators based on the ZBM. The synthesized ZBM was coated with tetraethyl orthosilicate for improving the hardness of the material. The adsorption of [99Mo]molybdate into ZBM was carried out by reacting ZBM into [99Mo]molybdate solution at 90°C to form ZBM-[99Mo] molybdate. ZBM-[99Mo]molybdate was then packed into generator column, then eluted with 10 × 1 mL of saline followed by 1 × 5 mL of NaOCl solution. The NaOCl solution concentrations used were 0.5%; 1%; 3%; and 5% for each column, respectively. This study resulted in a ZBM which has a 99Mo adsorption capacity of 167.5 ± 3.4 mgMo/g ZBM, as well as in a yield eluate of 99mTc of up to 70%, and the find that the optimum NaOCl concentration was 3%. The use of sodium hypochlorite solution affected 99Mo breakthrough. The higher sodium hypochlorite concentration used, the more 99Mo breaktrough exist on 99mTc eluate.Received: 22 October 2014; Revised: 21 April 2015; Accepted: 21 May 201