Pharmacokinetics Interaction and Biodistribution of 5 Fluorouracil with Radiopharmaceuticals 99mTc Glutathione for Cancer Diagnostic in Mice Cancer Model

Ahmad Kurniawan, Teguh Hafidz Ambar Wibawa, Isti Daruwati, Iswahyudi Iswahyudi

Abstract


Radiopharmaceutical 99mTc-Glutathione has been developed for cancer diagnostic in nuclear medicine. Interactions between chemotherapy drugs and radiopharmaceuticals can altered radiopharmaceuticals performance.  Drug interaction 5-fluorouracil (5-FU) with a radiopharmaceutical 99mTc-Glutathione in mice cancer model has been proven in pharmacokinetics study. The biological half-life distribution of 99mTc-Glutathione for cancer model mice when administrated with 5-FU become longer to 0.340±0.121h if compared with 99mTc-Glutathione. Biological half-life elimination for cancer model mice given with 99mTc-Glutathione is 72.712±2.427h. Administration of 5-FU makes the biological half-life elimination of 99mTc-Glutathione shorter to 17.030±3.459h. Biodistribution study of 5-FU continued with 99mTc-Glutathione for cancer model mice showed higher physiological uptake in the kidney was observed (39.77±2.70%ID/g) for 99mTc-Glutathione has lower uptake on kidney (29.55.3.73 %ID/g) with p<0.05. Based on calculation on cancer model mice with colon cancer compared with muscle, shown target/non-target (T/NT) ratio 2.93 for 5-FU continued with 99mTc-Glutathione has ratio 0.42. Low ratio T/NT may affect to poor organ visualization for cancer diagnosis.  Acute toxicity study has shown drugs safety for clinical purpose. The knowledge about chemotherapy drug interaction with a radiopharmaceutical is important to have a correct diagnosis of the patient on clinical application.


Keywords


5 Fluorouracil, 99mTc-Glutathione, Drug-Radiopharmaceutical Interaction, Cancer Diagnostic, Nuclear Medicine

Full Text:

PDF

References


Bray F., Ferlay J., Soerjomataram I., Siegel RL., Torre LA., Jemal A. 2018. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal For Clinicians, 68(6), 394-424. https://doi.org/10.3322/caac.21492.

Ercan MT., Senekowitsch-Schmidtke R., Bernatz, S., 1999. Biodistribution of 99m Tc-glutathione in mice with osteosarcoma : effect of gamma irradiation on tumour uptake. Research in Experimental Medicine, 359–367.

Focaccetti C., Bruno A., Magnani E., Bartolini D., Principi E., Dallaglio K., Albini A. 2015. Effects of 5-fluorouracil on morphology, cell cycle, proliferation, apoptosis, autophagy and ROS production in endothelial cells and cardiomyocytes. PloS one, 10(2). https://doi.org/10.1371/journal.pone.0115686.

Kim DW., Kim WH., Kim MH., Kim CG., Oh CS., Min JJ. 2014. Synthesis and evaluation of Tc-99m DTPA–glutathione as a non-invasive tumor imaging agent in a mouse colon cancer model. Annals of nuclear medicine, 28(5), 447-454. https://doi.org/10.1007/s12149-014-0835-8.

Longley DB., Harkin DP., Johnston PG. 2003. 5-Fluorouracil : Mechanisms of Action and Clinical Strategies. Nature review cancers, 3(5), 330–338. https://doi.org/10.1038/nrc1074.

Miura K., Kinouchi M., Ishida K., Fujibuchi W., Naitoh T., Ogawa H., Shibata C. 2010. 5-fu metabolism in cancer and orally-administrable 5-fu drugs. Cancers, 2(3), 1717-730. https://doi.org/10.3390/cancers2031717.

Mahendra I., Daruwati I., Halimah I., Pajrin SR. 2018. Pharmacokinetics Interaction of Non-Steroid Anti Inflammatory Drugs to 99m Tc-MDP Radiopharmaceuticals for Bone Imaging and Its Biodistribution. Atom Indonesia, 44(3), 173-177. https://doi.org/10.17146/aij.2018.741.

Nurlaila Z., Sriyani ME. 2010. Formulasi radiofarmaka 99mTc-glutation untuk diagnosis kanker. Jurnal Sains dan Teknologi Nuklir Indonesia, 11(2). http://dx.doi.org/10.17146/jstni.2010.11.2.399.

Perales JLG., Martínez AA. 2013. A portable database of adverse reactions and drug interactions with radiopharmaceuticals. Journal of nuclear medicine technology, 41(3), 212-215. https://doi.org/10.2967/jnmt.113.120626.

Razaq T., Nisar H., Roohi S., Shehzad A., Ahmad I. 2017. Administration of 99mTc-DTPA in combination with doxorubicin alters the radiopharmaceutical biodistribution in rats. Iranian Journal of Nuclear Medicine, 25(2), 122-128.

Santos-Oliveira R., Smith SW., Carneiro-Leão AMA. 2008. Radiopharmaceuticals drug interactions: a critical review. Anais da Academia Brasileira de Ciências, 80(4), 665-675. https://doi.org/10.1590/S0001-37652008000400008.

Saha GB. 2010. Radiopharmaceuticals and methods of radiolabeling. In Fundamentals of nuclear pharmacy (pp. 83-113). Springer, New York, NY.

Shuryak I., Dadachova E. 2015. New Approaches for Modeling Radiopharmaceutical Pharmacokinetics Using Continuous Distributions of Rates. Journal of Nuclear Medicine, 56(10), 1622-1628. https://doi.org/10.2967/jnumed.115.160515.

Silveira MB., Ferreira SM., Nascimento LT., Costa FM., Mendes BM., Ferreira AV., Mamede M. 2016. Preclinical acute toxicity, biodistribution, pharmacokinetics, radiation dosimetry and microPET imaging studies of [18F] fluorocholine in mice. Applied Radiation and Isotopes, 116, 92-101. https://doi.org/10.1016/j.apradiso.2016.07.021.

Tanaka T., Kohno H., Suzuki R., Yamada Y., Sugie S., Mori H. 2003. A novel inflammation‐related mouse colon carcinogenesis model induced by azoxymethane and dextran sodium sulfate. Cancer science, 94(11), 965-973.

Wahidin M., Noviani R., Hermawan S., Andriani V., Ardian A., Djarir H. 2012. Population-based cancer registration in Indonesia. Asian Pacific Journal of Cancer Prevention, 13(4), 1709-1710.

Wongso H., Zainuddin N., Iswahyudi I. 2013. Biodistribution and Imaging of The 99m Tc-Glutathione Radiopharmaceutical in White Rats Induced with Cancer. Atom Indonesia, 39(3), 106-111.

Zhang Y., Huo M., Zhou J., Xie S. 2010. PKSolver: An add-in program for pharmacokinetic and pharmacodynamic data analysis in Microsoft Excel. Computer methods and programs in biomedicine, 99(3), 306-314. https://doi.org/10.1016/j.cmpb.2010.01.007.




DOI: http://dx.doi.org/10.14499/indonesianjpharm30iss2pp91-97

Refbacks

  • There are currently no refbacks.




Copyright (c) 2019 Indonesian Journal of Pharmacy

Creative Commons License
This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.

Indonesian J Pharm indexed by:

web
analytics View My Stats