Effect of Gallium-68 isotope injection on hemoglobin derivatives concentrations after instant injection and its recovery in male rabbits (Oryctolagus cuniculus)
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Abstract
Oxidizing effects of ionizing radiation are well established and almost understood. However, exposure to low doses of widely used isotopes may result in minor and hidden oxidative stress in some forms of hemoglobin. This formation alteration regarding the legends of hemoglobin's stereochemical function may play a role in hemoglobin dysfunction. There are limited studies related to the effect of gallium isotope injections. The study intends to find the effect of gallium-68 isotope injection on male rabbits. It was conducted on thirty-two male rabbits (Orycytolagus cuniculus) divided into Group I: control and Group II: animals exposed to gallium-68 isotope at a similar dose commonly used in diagnostic protocols for humans. Blood samples were collected twice: the first was after two hours of injection with isotopes and the second was after twelve hours of injection. A linear, four-mathematical-equations matrix based on the Lamber-Beer law was used to measure the concentration of different hemoglobin derivatives. Results revealed a significant elevation (P<0.05) of methemoglobin, the oxidized form of hemoglobin, two hours after injection (Total hemoglobin = 4.463 ± 0.83), but this effect was completely reversed after twelve hours. This concluded that even low doses of isotopes result in oxidation of hemoglobin that recovers shortly. Furthermore, the outcome of the study supports the healthcare centres to understand the effect of gallium-68 injections on animals.
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Keywords
Derivatives, Gallium-68, Hemoglobin, Methemoglobin, Oxidative stress, Oxidation
References
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Blower, J. E., Ma, M. T., Al-Salemee, F. A. & Gee, A. D. (2021). The Hantzsch reaction for nitrogen-13 PET: preparation of [13 N] nifedipine and derivatives. Chemical Communications, 57(40), 4962-4965.
Breeman, W. A., de Jong, M., de Blois, E., Bernard, B. F., Konijnenberg, M. & Krenning, E. P. (2005). Radiolabelling DOTA-peptides with 68Ga. European Journal of Nuclear Medicine and Molecular Imaging, 32(4), 478-485.
Deppen, S. A., Liu, E., Blume, J. D., Clanton, J., Shi, C., Jones-Jackson, L. B., Lakhani, V., Baum, R.P., Berlin, J., Smith, G.T. & Walker, R. C. (2016). Safety and efficacy of 68Ga-DOTATATE PET/CT for diagnosis, staging, and treatment management of neuroendocrine tumors. Journal of Nuclear Medicine, 57(5), 708-714., doi: 10.2967/jnumed.115.163865.
Diaconu, V. (2009). Multichannel spectroreflectometry: a noninvasive method for assessment of on-line hemoglobin derivatives. Applied Optics, 48(10), D52-D61.
Eichendorff, S., Svendsen, P., Bender, D., Keiding, S. Christensen, E. I., Deleuran, B. & Moestrup, S. K. (2015). Biodistribution and PET imaging of a novel [68Ga]-anti-CD163-antibody conjugate in rats with collagen-induced arthritis and in controls. Molecular Imaging and Biology, 17(1), 87-93.
Gulcin, İ. (2020). Antioxidants and antioxidant methods: An updated overview. Archives of Toxicology, 94(3), 651-715.
Havas, M. (2017). When theory and observation collide: Can non-ionizing radiation cause cancer?. Environmental Pollution, 221(5), 501-505.
Hu, S., Qiao, C., Yuan, Z., Li, M., Ye, J., Ma, H., Wang, J., Xin. S. & Zhang, J. (2018). Therapy with high dose long-term antioxidant free radicals for severe paraquat poisoning: A pilot study. Experimental and Therapeutic Medicine, 16(6), 5149-5155.
Ighodaro, O. M. & Akinloye, O. A. (2018). First line defence antioxidants-superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX): Their fundamental role in the entire antioxidant defence grid. Alexandria Journal of Medicine, 54(4), 287-293.
Ilan, E., Velikyan, I., Sandström, M., Sundin, A. & Lubberink, M. (2020).Tumor-to-blood ratio for assessment of somatostatin receptor density in neuroendocrine tumors using 68Ga-DOTATOC and 68Ga-DOTATATE. Journal of Nuclear Medicine, 61(2), 217-221.Doi: 10.2967/jnumed.119.228072.
Kumar, D., Mathur, A., Prashant, V., Mirapurkar, S., Das, S., Kumar, S. & Murhekar, V. V. (2021). Regular production and supply of ready-to-use gallium-68 radiopharmaceuticals: centralized radiopharmacy concept with supply experience of 300 doses. Journal of Radioanalytical and Nuclear Chemistry, 330(1), 83-90.
Kumar, K. (2020). The current status of the production and supply of Gallium-68. Cancer Biotherapy & Radiopharmaceuticals, 35(3), 163-166.
Kumar, Y., Yadav, D. N., Ahmad, T. & Narsaiah, K. (2015). Recent trends in the use of natural antioxidants for meat and meat products. Comprehensive Reviews in Food Science and Food Safety, 14(6), 796-812.
Lenzo, N. P., Meyrick, D. & Turner, J. H. (2018). Review of gallium-68 PSMA PET/CT imaging in the management of prostate cancer. Diagnostics, 8(1), 10-16.
Lin, M., Waligorski, G. J. & Lepera, C. G. (2018). Production of curie quantities of 68Ga with a medical cyclotron via the 68Zn (p, n) 68Ga reaction. Applied Radiation and Isotopes, 133(2), 1-3.
Liu, Z., Ren, Z., Zhang, J., Chuang, C. C., Kandaswamy, E., Zhou, T., & Zuo, L. (2018). Role of ROS and nutritional antioxidants in human diseases. Frontiers in Physiology, 9(3),450-477.
Lourenço, S. C., Moldão-Martins, M. & Alves, V.D.(2019). Antioxidants of natural plant origins: From sources to food industry applications. Molecules, 12(4), 4110-4132.
Michiels, C., Raes, M., Toussaint, O. & Remacle, J. (1994). Importance of Se-glutathione peroxidase, catalase, and Cu/Zn-SOD for cell survival against oxidative stress. Free radical Biology and Medicine, 17(3), 235-248.
Minamimoto, R., Hancock, S., Schneider, B., Chin, F. T., Jamali, M., Loening, A. & Iagaru, A. (2016). Pilot comparison of 68Ga-RM2 PET and 68Ga-PSMA-11 PET in patients with biochemically recurrent prostate cancer. Journal of Nuclear Medicine, 57(4), 557-562.
Morishita, Y., Yamamoto, S., Izaki, K., Kaneko, J. H., Hoshi, K. & Torii, T. (2018). Optimization of thickness of GAGG scintillator for detecting an alpha particle emitter in a field of high beta and gamma background. Radiation Measurements, 112(4), 1-5.
Mu, L., Hesselmann, R., Oezdemir, U., Bertschi, L., Blanc, A., Dragic, M., Dirk, L., Christoph, S., Anaas, J. & Schibli, R. (2013). Identification, characterization and suppression of side-products formed during the synthesis of high dose 68Ga-DOTA-TATE. Applied Radiation and Isotopes, 76(4), 63-69.
Poeppel, T. D., Binse, I., Petersenn, S., Lahner, H., Schott, M., Antoch, G. & Boy, C. (2011). 68Ga-DOTATOC versus 68Ga-DOTATATE PET/CT in functional imaging of neuroendocrine tumors. Journal of Nuclear Medicine, 52(12), 1864-1870.
Redmer, B., Schargus, P., Karthikeyan, S., Nestler, B. & Müller, S. (2020). Determination of hemoglobin derivatives in unaltered whole blood samples using Support Vector regression in the spectral range from 450 to 700nm. In Optical Diagnostics and Sensing XX: Toward Point-of-Care Diagnostics, International Society for Optics and Photonics, 1(12), 470-485.
Sarangarajan R, Meera S, Rukkumani R, Sankar P, Anuradha G. (2017). Antioxidants: Friend or foe? Asian Pacific Journal of Tropical Medicine, 10(12):1111-1116. doi: 10.1016/j.apjtm.2017.10.017. Epub 2017 Oct 28. PMID: 29268965.
Song, X., Hou, C., Gao, Y., Zhu, J. & Zhang, D. (2018). Application of Hemoglobin and Its Derivatives in Food. Journal of Chinese Institute of Food Science and Technology. 18(4). 314-322. 10.16429/j.1009-7848.2018.07.038.
Spitz, D. R. & Hauer-Jensen, M. (2014). Ionizing radiation-induced responses: where free radical chemistry meets redox biology and medicine. Antioxidants & Redox Signaling, 20(9), 1407-1409.
Svedjehed, J., Pärnaste, M. & Gagnon, K. (2022). Demystifying solid targets: Simple and rapid distribution-scale production of [68Ga] GaCl3 and [68Ga] Ga-PSMA-11. Nuclear Medicine and Biology, 104(4), 1-10.
Tieu, W., Hollis, C. A., Kuan, K. K., Takhar, P., Stuckings, M., Spooner, N. & Malinconico, M. (2019). Rapid and automated production of [68Ga] gallium chloride and [68Ga] Ga-DOTA-TATE on a medical cyclotron. Nuclear Medicine and Biology, 74, 12-18.
Valko, M., Leibfritz, D., Moncol, J., Cronin, M. T., Mazur, M. & Telser, J. (2007). Free radicals and antioxidants in normal physiological functions and human disease. The International Journal of Biochemistry & Cell biology, 39(1), 44-84.
Van Kampen, E. J. & Zijlstra, W. G. (1983). Spectrophotometry of hemoglobin and hemoglobin derivatives. Advances in Clinical Chemistry, 23, 199-257.
Velikyan, I (2015). 68Ga-based radiopharmaceuticals: Production and application relationship, Molecules, 20(7), 12-35. doi: 10.3390/molecules200712913.
Wild, M., Folini, D., Schär, C., Loeb, N., Dutton, E. G. & König-Langlo, G. (2013). The global energy balance from a surface perspective. Climate Dynamics, 40(11), 3107-3134.
Yahyapour, R., Motevaseli, E., Rezaeyan, A., Abdollahi, H., Farhood, B., Cheki, M., Rezapoor, S., Shabeeb, D., Musa, A.E., Najafi, M. & Villa, V. (2018). Reduction–oxidation (redox) system in radiation-induced normal tissue injury: molecular mechanisms and implications in radiation therapeutics. Clinical and Translational Oncology, 20(8), 975-988.
Zulaikhah, S. T. (2017). The role of antioxidant to prevent free radicals in the body. Sains Medika, 8(1), 39-45.
Zwart, A., Buursma, A., Van Kampen, E. J. & Zijlstra, W. G. (1984). Multicomponent analysis of hemoglobin derivatives with reversed-optics spectrophotometer. Clinical Chemistry, 30(3), 373-379.
Zwart, A., Van Kampen, E. J. & Zijlstra, W. G. (1986). Results of routine determination of clinically significant hemoglobin derivatives by multicomponent analysis. Clinical Chemistry, 32(6), 972-978.
Attia, A.M., Ibrahim, F.A., Abd El-Latif, N.A., Aziz, S.W., Abdel mottaleb Moussa, S.A. & Elalfy, M.S. (2015). Determination of Human Hemoglobin Derivatives. Hemoglobin, 39(5), 371-384. doi: 10.3109/03630269.2015.1062775.
Blower, J. E., Ma, M. T., Al-Salemee, F. A. & Gee, A. D. (2021). The Hantzsch reaction for nitrogen-13 PET: preparation of [13 N] nifedipine and derivatives. Chemical Communications, 57(40), 4962-4965.
Breeman, W. A., de Jong, M., de Blois, E., Bernard, B. F., Konijnenberg, M. & Krenning, E. P. (2005). Radiolabelling DOTA-peptides with 68Ga. European Journal of Nuclear Medicine and Molecular Imaging, 32(4), 478-485.
Deppen, S. A., Liu, E., Blume, J. D., Clanton, J., Shi, C., Jones-Jackson, L. B., Lakhani, V., Baum, R.P., Berlin, J., Smith, G.T. & Walker, R. C. (2016). Safety and efficacy of 68Ga-DOTATATE PET/CT for diagnosis, staging, and treatment management of neuroendocrine tumors. Journal of Nuclear Medicine, 57(5), 708-714., doi: 10.2967/jnumed.115.163865.
Diaconu, V. (2009). Multichannel spectroreflectometry: a noninvasive method for assessment of on-line hemoglobin derivatives. Applied Optics, 48(10), D52-D61.
Eichendorff, S., Svendsen, P., Bender, D., Keiding, S. Christensen, E. I., Deleuran, B. & Moestrup, S. K. (2015). Biodistribution and PET imaging of a novel [68Ga]-anti-CD163-antibody conjugate in rats with collagen-induced arthritis and in controls. Molecular Imaging and Biology, 17(1), 87-93.
Gulcin, İ. (2020). Antioxidants and antioxidant methods: An updated overview. Archives of Toxicology, 94(3), 651-715.
Havas, M. (2017). When theory and observation collide: Can non-ionizing radiation cause cancer?. Environmental Pollution, 221(5), 501-505.
Hu, S., Qiao, C., Yuan, Z., Li, M., Ye, J., Ma, H., Wang, J., Xin. S. & Zhang, J. (2018). Therapy with high dose long-term antioxidant free radicals for severe paraquat poisoning: A pilot study. Experimental and Therapeutic Medicine, 16(6), 5149-5155.
Ighodaro, O. M. & Akinloye, O. A. (2018). First line defence antioxidants-superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX): Their fundamental role in the entire antioxidant defence grid. Alexandria Journal of Medicine, 54(4), 287-293.
Ilan, E., Velikyan, I., Sandström, M., Sundin, A. & Lubberink, M. (2020).Tumor-to-blood ratio for assessment of somatostatin receptor density in neuroendocrine tumors using 68Ga-DOTATOC and 68Ga-DOTATATE. Journal of Nuclear Medicine, 61(2), 217-221.Doi: 10.2967/jnumed.119.228072.
Kumar, D., Mathur, A., Prashant, V., Mirapurkar, S., Das, S., Kumar, S. & Murhekar, V. V. (2021). Regular production and supply of ready-to-use gallium-68 radiopharmaceuticals: centralized radiopharmacy concept with supply experience of 300 doses. Journal of Radioanalytical and Nuclear Chemistry, 330(1), 83-90.
Kumar, K. (2020). The current status of the production and supply of Gallium-68. Cancer Biotherapy & Radiopharmaceuticals, 35(3), 163-166.
Kumar, Y., Yadav, D. N., Ahmad, T. & Narsaiah, K. (2015). Recent trends in the use of natural antioxidants for meat and meat products. Comprehensive Reviews in Food Science and Food Safety, 14(6), 796-812.
Lenzo, N. P., Meyrick, D. & Turner, J. H. (2018). Review of gallium-68 PSMA PET/CT imaging in the management of prostate cancer. Diagnostics, 8(1), 10-16.
Lin, M., Waligorski, G. J. & Lepera, C. G. (2018). Production of curie quantities of 68Ga with a medical cyclotron via the 68Zn (p, n) 68Ga reaction. Applied Radiation and Isotopes, 133(2), 1-3.
Liu, Z., Ren, Z., Zhang, J., Chuang, C. C., Kandaswamy, E., Zhou, T., & Zuo, L. (2018). Role of ROS and nutritional antioxidants in human diseases. Frontiers in Physiology, 9(3),450-477.
Lourenço, S. C., Moldão-Martins, M. & Alves, V.D.(2019). Antioxidants of natural plant origins: From sources to food industry applications. Molecules, 12(4), 4110-4132.
Michiels, C., Raes, M., Toussaint, O. & Remacle, J. (1994). Importance of Se-glutathione peroxidase, catalase, and Cu/Zn-SOD for cell survival against oxidative stress. Free radical Biology and Medicine, 17(3), 235-248.
Minamimoto, R., Hancock, S., Schneider, B., Chin, F. T., Jamali, M., Loening, A. & Iagaru, A. (2016). Pilot comparison of 68Ga-RM2 PET and 68Ga-PSMA-11 PET in patients with biochemically recurrent prostate cancer. Journal of Nuclear Medicine, 57(4), 557-562.
Morishita, Y., Yamamoto, S., Izaki, K., Kaneko, J. H., Hoshi, K. & Torii, T. (2018). Optimization of thickness of GAGG scintillator for detecting an alpha particle emitter in a field of high beta and gamma background. Radiation Measurements, 112(4), 1-5.
Mu, L., Hesselmann, R., Oezdemir, U., Bertschi, L., Blanc, A., Dragic, M., Dirk, L., Christoph, S., Anaas, J. & Schibli, R. (2013). Identification, characterization and suppression of side-products formed during the synthesis of high dose 68Ga-DOTA-TATE. Applied Radiation and Isotopes, 76(4), 63-69.
Poeppel, T. D., Binse, I., Petersenn, S., Lahner, H., Schott, M., Antoch, G. & Boy, C. (2011). 68Ga-DOTATOC versus 68Ga-DOTATATE PET/CT in functional imaging of neuroendocrine tumors. Journal of Nuclear Medicine, 52(12), 1864-1870.
Redmer, B., Schargus, P., Karthikeyan, S., Nestler, B. & Müller, S. (2020). Determination of hemoglobin derivatives in unaltered whole blood samples using Support Vector regression in the spectral range from 450 to 700nm. In Optical Diagnostics and Sensing XX: Toward Point-of-Care Diagnostics, International Society for Optics and Photonics, 1(12), 470-485.
Sarangarajan R, Meera S, Rukkumani R, Sankar P, Anuradha G. (2017). Antioxidants: Friend or foe? Asian Pacific Journal of Tropical Medicine, 10(12):1111-1116. doi: 10.1016/j.apjtm.2017.10.017. Epub 2017 Oct 28. PMID: 29268965.
Song, X., Hou, C., Gao, Y., Zhu, J. & Zhang, D. (2018). Application of Hemoglobin and Its Derivatives in Food. Journal of Chinese Institute of Food Science and Technology. 18(4). 314-322. 10.16429/j.1009-7848.2018.07.038.
Spitz, D. R. & Hauer-Jensen, M. (2014). Ionizing radiation-induced responses: where free radical chemistry meets redox biology and medicine. Antioxidants & Redox Signaling, 20(9), 1407-1409.
Svedjehed, J., Pärnaste, M. & Gagnon, K. (2022). Demystifying solid targets: Simple and rapid distribution-scale production of [68Ga] GaCl3 and [68Ga] Ga-PSMA-11. Nuclear Medicine and Biology, 104(4), 1-10.
Tieu, W., Hollis, C. A., Kuan, K. K., Takhar, P., Stuckings, M., Spooner, N. & Malinconico, M. (2019). Rapid and automated production of [68Ga] gallium chloride and [68Ga] Ga-DOTA-TATE on a medical cyclotron. Nuclear Medicine and Biology, 74, 12-18.
Valko, M., Leibfritz, D., Moncol, J., Cronin, M. T., Mazur, M. & Telser, J. (2007). Free radicals and antioxidants in normal physiological functions and human disease. The International Journal of Biochemistry & Cell biology, 39(1), 44-84.
Van Kampen, E. J. & Zijlstra, W. G. (1983). Spectrophotometry of hemoglobin and hemoglobin derivatives. Advances in Clinical Chemistry, 23, 199-257.
Velikyan, I (2015). 68Ga-based radiopharmaceuticals: Production and application relationship, Molecules, 20(7), 12-35. doi: 10.3390/molecules200712913.
Wild, M., Folini, D., Schär, C., Loeb, N., Dutton, E. G. & König-Langlo, G. (2013). The global energy balance from a surface perspective. Climate Dynamics, 40(11), 3107-3134.
Yahyapour, R., Motevaseli, E., Rezaeyan, A., Abdollahi, H., Farhood, B., Cheki, M., Rezapoor, S., Shabeeb, D., Musa, A.E., Najafi, M. & Villa, V. (2018). Reduction–oxidation (redox) system in radiation-induced normal tissue injury: molecular mechanisms and implications in radiation therapeutics. Clinical and Translational Oncology, 20(8), 975-988.
Zulaikhah, S. T. (2017). The role of antioxidant to prevent free radicals in the body. Sains Medika, 8(1), 39-45.
Zwart, A., Buursma, A., Van Kampen, E. J. & Zijlstra, W. G. (1984). Multicomponent analysis of hemoglobin derivatives with reversed-optics spectrophotometer. Clinical Chemistry, 30(3), 373-379.
Zwart, A., Van Kampen, E. J. & Zijlstra, W. G. (1986). Results of routine determination of clinically significant hemoglobin derivatives by multicomponent analysis. Clinical Chemistry, 32(6), 972-978.
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How to Cite
Effect of Gallium-68 isotope injection on hemoglobin derivatives concentrations after instant injection and its recovery in male rabbits (Oryctolagus cuniculus). (2022). Journal of Applied and Natural Science, 14(2), 677-683. https://doi.org/10.31018/jans.v14i2.3482
