Study of Ligand Exchange Reaction of Bis-(N-(2,6-Dimethylphenyl Carbamoylmethyl)Iminodiaceto) Technetate (III) Complex Ion with Anticancer Drug Bleomycin
Abstract
A molecule of an anticancer drug such as bleomycin (Blm) could replace N-(2,6-dimethylphenylcarbamoyl methyl) iminodiacetic acid (HIDA) bound to technetium (III), yielding technetium-99m-bleomycin (99mTc-Blm) complex ion. The experimental results showed that a stable 99mTc-Blm could be prepared by the ligand exchange reaction between bis-(N-(2,6-dimethylphenylcarbamoylmethyl) iminodiaceto) technetate (III) ion and Blm under acidic condition (pH < 3) at 100 oC and the HIDA : Blm mole ratio of 1 : 1. The radiochemical purity of 99mTc-Blm at pH 7.4 was found to remain higher than 95% within 3 hours, allowing this complex ion to be a potential candidate for use as a cancer imaging agent. Keywords : Technetium-99m, Bleomycin, ligand Exchange, complex Ion, radio-imaging agentReferences
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Costello CE, Brodack JW, Jones AG, Davison A, Johnson DL, Kasina S, Fritzberg AR. (1983) The investigation of radiopharmaceutical components by fast atom bombardment mass spectrometry : The identification of Tc-HIDA and the epimers of Tc-CO2DADS. J. Nucl. Med. ,24(4), 353-355.
Dabrowiak J.C. (1980) The coordination chemistry of bleomycin : A review. J. Inor. Biochem. ,13, 317-337.
Horiuchi K., Yokoyama A., Fujibayashi Y., Tanaka H., Odori T., Saji H., Morita R., Torizuka K. (1981) Tin-adsorbed resin for the preparation of 99mTc-radiopharmaceuticals: Stable complex of 99 mTc-bleomycin.
Int. J. App. Radiat. Iso. , 32(1), 47-52.
Iitaka Y, Nakamura H, Nakatani T, Muraoka Y, Fujii A, Takita T, Umezawa H. (1978). Chemistry of bleomycin. XX. The X-ray structure determination of P-3A Cu(II)-complex a biosynthetic intermediate of bleomycin.
J Antibiot (Tokyo). , 31(10),1070-1072.
Kosjek T., Krajnc A., Gornik T., Zigon D., Groselj A., Sersa G., Cemazar M. (2016). Identification and quantification of bleomycin in serum and tumor tissue by liquid chromatography coupled to high resolution mass spectrometry, Talanta, 160, 164-171,
Loberg MD., Fields AT. (1977) Stability of 99mTc-labeled N-substituted iminodiacetic acids: Ligand exchange reaction between 99mTc-HIDA and EDTA. Int. J. App. Radiat. Iso., 28(8), 687-692.
Loberg MD., Fields AT. (1978) Chemical structure of technetium-99m-lebeled N-(2,6-dimethylphenyl carbamoylmethyl)-iminodiacetic acid (Tc-HIDA) Int. J. App. Radiat. Iso., 29(3), 167-173.
Mori T, Hamamoto K, Onoyama Y, Torizuka K. (1975) Tumor imaging after administration of 99mTc-labeled bleomycin. J. Nucl. Med., 16, 414-422.
Oppenheimer, N. J., Rodriguez, L. O., & Hecht, S. M. (1979). Structural studies of of “active complex” of bleomycin: assignment of ligands to the ferrous ion in a ferrous-bleomycin-carbon monoxide complex. Proceedings of the National Academy of Sciences of the United States of America, 76(11), 5616–5620.
Raban P, Brousil J, Svihovcová P. (1979) Chemical and biological properties of bleomycin labelled with 57Co. Eur. J. Nucl. Med. ,4, 191-197.
Stubbe J., and Kozarich JW. (1987) Mechanisms of bleomycin-induced DNA degradation. Chem. Rev. 87(5), 1107-1136.
Sugiura Y., Ishizu K., Miyoshi K. (1976) Studies of metallobleomycins by electronic spectroscopy, electron spin resonance spectroscopy, and potentiometric titration. J. Antibiotics (Tokyo)., 29, 1102-1108
Umezawa H, Maeda K, Takeuchi T, Okami Y. (1962) New antibiotics bleomycin A and B. J. Antibiot (Tokyo).,
19, 200-209.
Wistow BW, Subramanian G, Heertum RL, Henderson RW, Gagne GM, Hall RC, McAfee JG. (1977) An evaluation of 99mTc-labeled hepatobiliary agents. J. Nucl. Med., 18(5),455-461.
Yokoyama A., Terauchi Y.i, Horiuchi K., Okumura S., Saito Y., Tanaka H., Odori T., Morita R., Mori T., Torizuka K. (1978) The importance of the chemical state of 99mTc radiopharmaceticals : an effetive tumor imaging form of 99mTc bleomycin. Int. J. App. Radiat. Iso. ,29, 549-555.
6094-6101
Costello CE, Brodack JW, Jones AG, Davison A, Johnson DL, Kasina S, Fritzberg AR. (1983) The investigation of radiopharmaceutical components by fast atom bombardment mass spectrometry : The identification of Tc-HIDA and the epimers of Tc-CO2DADS. J. Nucl. Med. ,24(4), 353-355.
Dabrowiak J.C. (1980) The coordination chemistry of bleomycin : A review. J. Inor. Biochem. ,13, 317-337.
Horiuchi K., Yokoyama A., Fujibayashi Y., Tanaka H., Odori T., Saji H., Morita R., Torizuka K. (1981) Tin-adsorbed resin for the preparation of 99mTc-radiopharmaceuticals: Stable complex of 99 mTc-bleomycin.
Int. J. App. Radiat. Iso. , 32(1), 47-52.
Iitaka Y, Nakamura H, Nakatani T, Muraoka Y, Fujii A, Takita T, Umezawa H. (1978). Chemistry of bleomycin. XX. The X-ray structure determination of P-3A Cu(II)-complex a biosynthetic intermediate of bleomycin.
J Antibiot (Tokyo). , 31(10),1070-1072.
Kosjek T., Krajnc A., Gornik T., Zigon D., Groselj A., Sersa G., Cemazar M. (2016). Identification and quantification of bleomycin in serum and tumor tissue by liquid chromatography coupled to high resolution mass spectrometry, Talanta, 160, 164-171,
Loberg MD., Fields AT. (1977) Stability of 99mTc-labeled N-substituted iminodiacetic acids: Ligand exchange reaction between 99mTc-HIDA and EDTA. Int. J. App. Radiat. Iso., 28(8), 687-692.
Loberg MD., Fields AT. (1978) Chemical structure of technetium-99m-lebeled N-(2,6-dimethylphenyl carbamoylmethyl)-iminodiacetic acid (Tc-HIDA) Int. J. App. Radiat. Iso., 29(3), 167-173.
Mori T, Hamamoto K, Onoyama Y, Torizuka K. (1975) Tumor imaging after administration of 99mTc-labeled bleomycin. J. Nucl. Med., 16, 414-422.
Oppenheimer, N. J., Rodriguez, L. O., & Hecht, S. M. (1979). Structural studies of of “active complex” of bleomycin: assignment of ligands to the ferrous ion in a ferrous-bleomycin-carbon monoxide complex. Proceedings of the National Academy of Sciences of the United States of America, 76(11), 5616–5620.
Raban P, Brousil J, Svihovcová P. (1979) Chemical and biological properties of bleomycin labelled with 57Co. Eur. J. Nucl. Med. ,4, 191-197.
Stubbe J., and Kozarich JW. (1987) Mechanisms of bleomycin-induced DNA degradation. Chem. Rev. 87(5), 1107-1136.
Sugiura Y., Ishizu K., Miyoshi K. (1976) Studies of metallobleomycins by electronic spectroscopy, electron spin resonance spectroscopy, and potentiometric titration. J. Antibiotics (Tokyo)., 29, 1102-1108
Umezawa H, Maeda K, Takeuchi T, Okami Y. (1962) New antibiotics bleomycin A and B. J. Antibiot (Tokyo).,
19, 200-209.
Wistow BW, Subramanian G, Heertum RL, Henderson RW, Gagne GM, Hall RC, McAfee JG. (1977) An evaluation of 99mTc-labeled hepatobiliary agents. J. Nucl. Med., 18(5),455-461.
Yokoyama A., Terauchi Y.i, Horiuchi K., Okumura S., Saito Y., Tanaka H., Odori T., Morita R., Mori T., Torizuka K. (1978) The importance of the chemical state of 99mTc radiopharmaceticals : an effetive tumor imaging form of 99mTc bleomycin. Int. J. App. Radiat. Iso. ,29, 549-555.
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2017-05-11
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