Biological Safety Evaluation of 99mTc-DTPA-Ketoconazole for Diagnosis of Fungal Infection
Keywords:
Fungal infection, 99mTc-DTPA-Ketoconazole, Biological safety evaluation, Toxicity, Sterility, Apirogenicity
Abstract
Infectious diseases have become one of the leading cause of mortality around the world, including in the Southeast Asia. One of the microbial that cause infection is fungi. Occasionally, deep-seated fungal infection is difficult to detect using conventional diagnosis methods and therefore leads to inaccurate detection. Our previous research was conducted in order to obtain the labeled compound of 99mTc-DTPA-Ketoconazole with a high radiochemical purity (98.40 ± 0.86%). Moreover, the in-vitro assays showed that 99mTc-DTPA-Ketoconazole can potentially bind to Candida albicans. On the other hand, in clinical routine use, diagnostic kit should be safe for the patients. Consequently, this research was conducted to determine the biological safety parameters of 99mTc-DTPA-Ketoconazole on the animal study, including single dose and acute toxicity test, sterility, and apirogenicity test. The results showed that both the single dose at 34.6 μCi and dose until 149 times of the single dose did not stimulate the toxic response to the animals. In addition, the sterility data revealed that there was no microbial growth after 7 days of incubation at 37°C as well as fungal growth after 14 days of incubation at 25°C. Furthermore, the apirogenicity test using rabbits revealed that there was no increase in temperature more than 0.6°C for each animal and not more than 1.5°C of total increase of temperature for all the animals. It is concluded that the 99mTc-DTPA-Ketoconazole is satisfy the requirements of biological safety of a radiopharmaceutical and therefore was acceptable for fungal detection in nuclear medicine.Downloads
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Awaludin, R. (2011). Radioisotop Teknesium-99m dan Kegunaanya. Retrieved February 20, 2014, from http://www.infonuklir.com/filedownload/Radioisotop dan Radiofarmaka untuk Berbagai Keperluan.pdf.
Dass, S. S., Hall, A. V., Wareham, D. W., Britton, K. E. (2002). Infection imaging with radiopharmaceuticals in the 21th century,. Brazilian Archives of Biology.
Foxman, B. (2011). Infectious diseases. IARC Scientific Publications, (163), 421–440.
Halimah, I., Sumpena, Y., Sugiharti, R. J., & Misyetti. (2009). Uji Toksisitas Akut Radiofarmaka 99mTc-CTMP Pada Mencit (Mus musculus). Prosiding Seminar Nasional Sains Dan Teknologi Nuklit, 347–351.
Hendris wongso, & Halimah, I. (2013). PRINSIP UJI PRAKLINIS DAN KLINIS DALAM PENGEMBANGAN RADIOFARMAKA PENYIDIK KANKER. In SEMINAR NASIONAL VIII SDM TEKNOLOGI NUKLIR (pp. 334–339). yogyakarta.
Juwita, R., Kartini, N., Toksisitas, U. J. I., Pada, R. T., Mus, M., Test, T., … Mice, T. I. N. (2007). UJI TOKSISITAS RADIOFARMAKA Tc- ETAMBUTOL PADA MENCIT ( Mus musculus ), 17–18.
Kaul, A., Hazari, P. P., Rawat, H., Singh, B., Kalawat, T. C., Sharma, S., … Mishra, A. K. (2013). International Journal of Infectious Diseases Preliminary evaluation of technetium-99m-labeled ceftriaxone : infection imaging agent for the clinical diagnosis of orthopedic infection. International Journal of Infectious Diseases, 17(4), e263–e270. http://doi.org/10.1016/j.ijid.2012.10.011
Kementerian Kesehatan Republik Indonesia. (2014). Farmakope Indonesia (V). Jakarta: Dirjen Bina Kefarmasian dan Alat Kesehatan.
Maula Eka Sriyani, Desty Eltiana Ibrahim, Rizky Juwita S., A. H. W. (2015). PENENTUAN UPTAKE CANDIDA ALBICANS TERHADAP SEBAGAI KIT DIAGNOSTIK PENYAKIT INFEKSI FUNGI. Prosiding Seminar Nasional Teknologi Energi Nuklir 2015.
Motaleb, M. A., El-Kolaly, M. T., Ibrahim, A. B., E.-B. A. A. (2011). Study on the preparation and biological evaluation of 99mTc-gatifloxacin and 99mTc-cefepime complexes. Hungaria: Akadēmiai Kiadό.
Moustapha, M. E., & Shweeta, H. A. (2016). Technetium-labeled danofloxacin complex as a model for infection imaging. ARABIAN JOURNAL OF CHEMISTRY. http://doi.org/10.1016/j.arabjc.2014.10.017
Oh, K., Yamada, K., Asami, T., & Yoshizawa, Y. (2012). Synthesis of novel brassinosteroid biosynthesis inhibitors based on the ketoconazole scaffold. Bioorganic and Medicinal Chemistry Letters, 22(4), 1625–1628. http://doi.org/10.1016/j.bmcl.2011.12.120
Owunwanne A, Patel M, Sadek S. (1995). The Handbook of Radiopharmaceutical (1st ed.). London: Chapman & Hall Medical.
Roberta, S., Rodrigues, C., Luís, A., Barros, B. De, Serakides, R., Odília, S., … Andrade, R. De. (2015). Identi fi cation of Staphylococcus aureus infection by aptamers directly radiolabeled with technetium-99m. Nuclear Medicine and Biology, 42(3), 292–298. http://doi.org/10.1016/j.nucmedbio.2014.12.002
Saha, G. B. (2010). fundamentals of nuclear pharmacy (Sixth). Cleveland: Springer.
Schwochau, K. (2000). Technetium Chemistry and Radiopharmaceutical Aplications. Germany: Wi Ley-VCH.
Sriyani, M. E., Ibrahim, S., & Hanafiah, a. (2013). OPTIMALISASI PENANDAAN 99mTc-DTPA-KETOKONAZOL SEBAGAI RADIOFARMAKA UNTUK DETEKSI INFEKSI FUNGI. Jurnal Penelitian, 04, 11–22.
Sriyani, M. E., & Ws, A. H. (n.d.). Physicochemical Characteristic of 99m Tc-DTPA-ketoconazole as a Radiopharmaceutical for Deep Seated Fungal Detection ISBN : 978-979-96595-4-5 ISBN : 978-979-96595-4-5, (71), 978–979.
Tjay, T. H., & Rahardja, K. (2007). Obat-obat Penting. Khasiat, Penggunaan dan Efek-efek Sampingnya (6th ed.). Jakarta: PT. Elex Media Komputindo.
Verbruggen, A. M. (2007). TECHNETIUM-99m RADIOPHARMACEUTICALS Current Situation and Perspectives. Belgia: Laboratory of Radiopharmacy, Katholieke Universiteit Leuven,.
Welling, M., Ferro-Flores, G., & Pirmettis, I. (2009). Technetium-99m Labelled Infection Imaging Agents. Technetium-99m Radiopharmaceuticals: Status and Trends, (1), 137–156. Retrieved from http://www-pub.iaea.org/MTCD/publications/PDF/Pub1405_web.pdf
Yazdani, A., Pitchunmony, T. S., Banevicius, L., Czorny, S., & Valliant, J. F. (2014). Characterization of 99mTc-caspofungin as fungal infection agent and assessment of potential influence of pretreatment. Nuclear Medicine and Biology, 41(7), 616. http://doi.org/10.1016/j.nucmedbio.2014.05.093
Z, Nurlaila., Basry, H. T., Iljas, R., Suminar, R, M. (2005). Karakterisasi radiofarmaka 99mTc-siprofloksasin sebagai penyidik infeksi. Majalah Farmasi Indonesia, 16(4), 217.
Zolle, I. (2007). Technetium-99m Pharmaceuticals. New York: Springer.
Published
2017-02-28
How to Cite
Sriyani, M., Wongso, H., Widyasari, E., Sugiharti, R., Halimah, I., Iswahyudi, I., Sidik, A., Isabela, E., & Nuraeni, W. (2017). Biological Safety Evaluation of 99mTc-DTPA-Ketoconazole for Diagnosis of Fungal Infection. Indonesian Journal of Physics and Nuclear Applications, 2(1), 1-8. https://doi.org/https://doi.org/10.24246/ijpna.v2i1.1-8
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This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
Indonesian Journal of Physics and Nuclear Applications is licensed under a Creative Commons Attribution 4.0 International License.
