89Zr'un Proton Hızlandırıcıda Üretim Koşullarının İncelenmesi

Yıl 2019, Cilt: 40 Sayı: 2, 388 - 395, 30.06.2019

Buğra Gökhun Bulduk Perihan Ünak Ayfer Yurt Kılçar Özge Kozguş Güldü Volkan Tekin

https://doi.org/10.17776/csj.448616

Öz

⁸⁹Zr,
uygun bozunum özellikleri, fiziksel yarı ömrü (t1/2 ~ 78 saat) nedeniyle artan
ilgi görmüştür ve bu nedenle de antikor temelli immüno-PET için uygun
görülmektedir. Relatif olarak salınan pozitronların düşük bozunum enerjisi
yüksek çözünürlüklü görüntü alınmasını sağlar. ⁸⁹Zr-işaretli
radyofarmasötiklerinin insanda kullanımı özellikle ⁸⁹Zr işaretli
antikorlar olarak immuno-PET de kullanımı günden güne artmaktadır.

Bu çalışmada, ⁸⁹Zr
üretimi ile ilgili hesaplamalar yapılmış ve ⁸⁹Y hedef sisteminin
kullanıldığı (p, n) reaksiyonu kullanılmıştır. Bunun için reaksiyon sonucu Bağ
Enerjisi, Eşik Enerjisi, Minimum Coulomb Bariyeri Enerjisi hesaplanmış, daha
sonra bu reaksiyonun tesir kesitleri Empire3.2/MALTA kodu kullanılarak
bulunmuştur. Işınlama hesaplamaları belirlendikten sonra proton bombardımanı
yapılmıştır. Bu ışınlama Ankara Sarayköy Nükleer Araştırma ve Eğitim
Merkezi'ndeki proton hızlandırıcısında gerçekleştirilmiştir. Kullanılan
siklotron IBA tipi Siklon-30'dur. Daha sonra ayırma kısmı Dowex reçine sistemi
ile yapılmıştır. Işınlanmış ⁸⁹Zr, hedef sistemden ayrıldıktan sonra,
radyoaktif ⁸⁹Zr saf olarak elde edilmiştir.

Anahtar Kelimeler

89Zr, Siklon-30, Empire3.2/MALTA, Radyonüklid, Dowex

Analyzing of Production Conditions of 89Zr in the Particle Accelerator

Öz

Nowadays 89Zr is outstanding PET radionuclide
with its physical half-life (t1/2 ~ 78 hours), useful decay specifications and
so that it is suitable for antibody-based immuno-PET. Relatively oscillated
positrons' low decay energies supply to take high-resolution. 89Zr-labeled
radiopharmaceuticals, especially as 89Zr-labeled antibodies applications are
getting increase day by day.

In this study, calculations about production of 89Zr were
done and used (p,n) reaction of 89Y target system. For this Q-value, Threshold
Energy, Minimum Coulomb Barrier Energy of the reaction were calculated then the
cross-sections of this reaction were found using Empire3.2/MALTA code. After
determining the irradiation calculations, the bombardment performed. The
irradiation was performed in Ankara Sarayköy Nuclear Research and Training
Center, proton accelerator. The cyclotron is IBA type Cyclone-30. Then
separation part was done with Dowex resine system. After separation 89Zr from
the irradiated target system, radioactive 89Zr was obtained purely.

Anahtar Kelimeler

89Zr, Cyclone-30, Empire3.2/MALTA, Radionuclide, Dowex, PET Radionuclides

Kaynakça

• Adonai N., Nguyen K.N., Walsh J., Iyer M., Toyokuni T., Phelps M.E., McCarthy T., McCarthy D.W. and Gambhir S.S., Ex-vivo Cell Labeling with 64Cu-pyruvaldehyde-bis(N4-methylthiosemicarbazone) for Imaging Cell Trafficking in Mice with Positron Emission Tomography, Proc. Natl. Acad. Sci. U.S.A., 5 (2002), 99(5), 3030-3035.
• Aerts H.J.W.L., Dubois L., Perk L., Vermaelen P., van Dongen G.A.M.S., Wouters B.G. and Lambin P., Disparity Between in-vivo EGFR Expression and 89Zr Labeled Cetuximab Uptake Assessed with PET, J. Nucl. Med., 50 (2009), 123–131.
• Alfuraih A., Alzimami K., Ma A.K. and Alghamdi A, Optimization of 89Zr Production Using Monte Carlo Simulations, J. Radioanal. Nucl. Chem., 296 (2013), 1025–1029.
• Avila-Rodriguez M.A., Selwyn R.G., Converse A.K. and Nickles R.J., 86Y and 89Zr as PET Imaging Surrogates for 90Y: A Comparative Study, Proceedings of Ninth Mexican Symposium on Medical Physics, (2006) pp 45–47.
• Becker W., Emmrich F., Horneff G., Burmester G., Seiler F., Schwarz A., Kalden J. and Wolf F., Imaging Rheumatoid Arthritis Specifically with Technetium-99m CD4-specific (T-helper lymphocytes) Antibodies, Eur. J. Nucl. Med., 17, (1990), 156159.
• Borjesson P.K.E., Jauw Y.W.S., de Bree R., Roos J.C., Castelijns J., Leemans C.R., van Dongen G.AM.S. and Boellaard R., Radiation Dosimetry of 89Zr-Labeled Chimeric Monoclonal Antibody U36 as Used for Immuno-PET in Head and Neck Cancer Patients, J. Nucl. Med., 50(11), (2009), 1828–1836.
• Borjesson P.K.E., Jauw Y.W.S., Boellaard R., de Bree R., Comans E.F.I., Roos J.C., Castelijns J.A., Vosjan M.J., Kummer J.A., Leemans C.R., Lammertma A.A. and van Dongen G.A., Performance of Immuno-Positron Emission Tomography with Zirconium-89-Labeled Chimeric Monoclonal Antibody U36 in the Detection of Lymph Node Metastases in Head and Neck Cancer Patients, Clinical Cancer Research, 12 (2006), 2133-2140.
• Dijkers E.C., Oude Munnink T.H., Kosterink J.G., Brouwers A.H., Jager P.L., de Jong J.R., van Dongen G.A., Schröder C.P., Lub-de Hooge M.N. and de Vries E.G., Biodistribution of 89Zr-Trastuzumab and PET Imaging of HER2-Positive Lesions in Patients with Metastatic Breast Cancer, Clin. Pharmacol. Ther., 87 (2010), 586–592.
• Dijkers E.C.F., Kosterink J.G.W., Rademaker A.P., Perk L.R., van Dongen G.A.M.S., Bart J., de Jong J.R., de Vries E.G.E. and Lub-de Hooge M.N., Development and Characterization of Clinical-Grade 89Zr-Trastuzumab for HER2/neu ImmunoPET Imaging, J. Nucl. Med., 50 (2009), 974–981.
• Disselhorst J.A., Brom M., Laverman P., Slump C.H., Boerman O.C., Oyen W.J.G., Gotthardt M. and Visser E.P., Image-Quality Assessment for Several Positron Emitters Using the NEMA NU 4-2008 Standards in the Siemens Inveon Small Animal PET Scanner, J. Nucl. Med., 51 (2010), 610617.
• Firestein G.S., Evolving Concepts of Rheumatoid Arthritis, Nature 423 (6937), 35636115 (2003).
• Holland J.P., Sheh Y. and Lewis J.S., Standardized Methods for the Production of High Specific-Activity Zirconium-89, Nucl. Med. Biol., 36 (2009), 729–739.
• IAEA, IAEA-TRS-468: Cyclotron Produced Radionuclides: Physical Characteristics and Production Methods, (2009), Vienna.
• Lampropoulou V., Calderon-Gomez E., Roch T., Neves P., Shen P., Stervbo U., Boudinot P., Anderton S.M. and Fillatreau S., Suppressive Functions of Activated B Cells in Autoimmune Diseases Reveal the Dual Roles of Toll-like Receptors in Immunity, Immunol. Rev., 233 (2010), 146161.
• Malviya G., Vries E.F.J.D., Dierckx R.A. and Signore, A., Radiopharmaceuticals for Imaging Chronic Lymphocytic Inflammation. Braz. Arch. Biol. Technol., 50 (2007), 1–13.
• Meijs W.E., Haisma H.J., Klok R.P., van Gog F.B., Kievit E., Pinedo H.M. and Herscheid J.D., Zirconium-Labeled Monoclonal Antibodies and Their Distribution in Tumor-Bearing Nude Mice, J. Nucl. Med., 38 (1997), 112–118.
• Nayak T.K. and Brechbiel M.W., Radioimmunoimaging with Longer-Lived Positron-Emitting Radionuclides: Potentials and Challenges, Bioconjugate Chem., 20 (2009), 825–841.
• Perk L.R., Visser O.J., van Walsum M.S., Vosjan M.J.W.D., Visser G.W.M., Zijlstra J.M., Huijgens P.C. and van Dongen G.A.M.S., Preparation and Evaluation of (89)Zr-Zevalin for Monitoring of (90)Y-Zevalin Biodistribution with Positron Emission Tomography, Eur. J. Nucl. Med. Mol. Imaging, 33 (2006), 1337–1345.
• Toh M.L. and Miossec, P., The Role of T Cells in Rheumatoid Arthritis: New Subsets and New Targets, Curr. Opin. Rheumatol., 19 (2007), 284288.
• Van Dongen G.A.M.S., Visser G.W.M., Hooge M.N.L., De Vries E.G. and Perk L., Immuno-PET: a Navigator in Monoclonal Antibody Development and Applications, The Oncologist, 12 (2007), 1379–1389.
• Verel I., Visser G.W.M., Boellaard R., van Walsum M.S., Snow G.B. and van Dongen G.A.M.S., 89Zr Immuno-PET: Comprehensive Procedures for the Production of 89Zr-Labeled Monoclonal Antibodies, J. Nucl. Med., 44 (2003), 1271–1281.
• Verel I., Visser G.W.M. and van Dongen G.A.M.S., The Promise of Immuno-PET in Radioimmunotherapy, J. Nucl. Med., 46 (2005), 164s–171s.
• Walther M., Gebhardt P., Grosse-Gehling P., Wurbach L., Irmler I., Preusche S., Khalid M., Opfermann T., Kamradt T., Steinbach J. and Saluz H.P., Implementation of 89Zr Production and In-vivo Imaging of B-cells in Mice with 89Zr-Labeled Anti-B-Cell Antibodies by Small Animal PET/CT, Applied Radiation and Isotopes, 69 (2011), 852–857.
• Wu A.M., Antibodies and Antimatter: the Resurgence of Immuno-PET, J. Nucl. Med., 50 (2009)..