Preparation and biological evaluation of 99mTc tricarbonyl cysteine

테크네슘-99엠 트리카보닐 시스테인의 제조 및 생물학적 특성 평가

  • Jang, Beom-su (College of Vetetinary Medicine, Chungnam National University) ;
  • Park, Kyung-bae (Division of Radioisotope Production and Application, Korea Atomic Energy Research Institute) ;
  • Yun, Hyo-in (College of Vetetinary Medicine, Chungnam National University)
  • 장범수 (충남대학교 수의과대학) ;
  • 박경배 (한국원자력연구소 동위원소이용연구부) ;
  • 윤효인 (충남대학교 수의과대학)
  • Accepted : 2004.02.23
  • Published : 2004.03.31


This paper describes the development of $^{99m}Tc$ tricarbonyl cysteine as potential renal function diagnostic radiopharmaceutical and evaluation of its biological characteristics using experimental animals. l-Cysteine was labeled efficiently with $^{99m}Tc$ tricarbonyl precursor $([^{99m}Tc(CO)_3(H_2O)_3)]^{+})$ under 30 min heating at ${75^{\circ}C}$. Labeling yield and stability were analyzed by high performance liquid chromatography (HPLC). The biodistribution property of $^{99m}Tc$ tricarbonyl cysteine in mice and its dynamic imaging profiles in rabbits were carried out. To investigate the excretion mechanism of $^{99m}Tc$ tricarbonyl cysteine, tubular transport inhibition test with probenecid was adopted. $^{99m}Tc$ tricarbonyl cysteine was obtained with a high labeling yield under the moderate condition. The results of biodistribution experiments of $^{99m}Tc$ tricarbonyl cysteine in ICR mice at 3 and 90 min provided that $^{99m}Tc$ tricarbonyl cysteine was very highly accumulated in the kidney and bladder, thereby almost 99% of $^{99m}Tc$ tricarbonyl cysteine was excreted within 90 min post injection. The same results were confirmed by the whole body dynamic images for 30 minutes and static images in rabbits at given time intervals after injection. Renogram of $^{99m}Tc$ tricarbonyl cysteine in rabbits showed that its $T_{max}$ and $T_{1/2}$ of $^{99m}Tc$ tricarbonyl cysteine were $2.33{\pm}0.56$ and $4.30{\pm}0.79$ min, respectively. The $T_{max}$ of $^{99m}Tc$ tricarbonyl cysteine with probenecid pretreatment was $2.30{\pm}0.17$ min, whereas $T_{1/2}$ of that with probenecid pretreatment was $17.0{\pm}32.47$ min. $T_{1/2}$ of $^{99m}Tc$ tricarbonyl cysteine with probenecid pretreatment was significantly different, as compared to the result without probenecid (p<0.0001). The results showed that the excretion of $^{99m}Tc$ tricarbonyl cysteine was extremely affected by probenecid. Therefore, $^{99m}Tc$ tricarbonyl cysteine was rapidly excreted from the kidney principally by the tubular secretion.


Supported by : Ministry of Science and Technology (MOST)


  1. Alberto, R., Schibli, R., Egli, A., Schubiger, P. A., Herrmann, W. A., Artus, G., Abram, U. and Kaden, T. A. Metal carbonyl syntheses X XII. low pressure carbonylation of $[MOCl_4]- and [M_4]^-$ : the technetium(I) and rhenium(I) complexes $[NEt_4]_2[MCl_3(CO)_3]$/. J. Organomet. Chem. 1995, 493, 119-127
  2. Alberto, R., Schibli, R., Abram, U., Egli, A., Knapp, F. F. and Schubiger, P. A. Potential of the $'[M(CO)_3]^+'$ (M=Re, Tc) moiety for the labelling of biomolecules. Radiochimica Acta. 1997, 79, 99-103
  3. Alberto, R., Schibli, R., Egli, A. and Schubiger, P. A. A novel organometallic complex of technetium for labeling of biomolecules: synthesis of $[{99m}^Tc(H_2O)_3(CO)_3]^+ from [{99m}TcO_4]^-$ in aqueous solution and its reaction with a bifunctional ligand. J. Am. Chem. Soc. 1998, 120, 7987-7988
  4. Bonnyman, J. Preparation and biological behaviour of $^{99m}Tc-carbonyl and ^{99m} Tc-nitrido$ complexes of cysteine and some cysteine esters. Nucl. Med. Biol. 1995, 22, 943-948
  5. Bowen, B. M., Henderson, D. R., Kellam, J. and Wood, D. E. $^{99m}Tc-$cysteine- An agent for renal scintigraphy. Am. J. Hosp. Pharm. 1972, 29, 502
  6. Bubeck, B., Brandau, W., Weber, E., Kalble, T., Pareckh, N. and Georgi, P. Pharmacokinetics of Technetium-99m-$MAG_3$ in human. J. Nucl. Med. 1990, 31, 1285-1293
  7. Bubeck, B., Brandau, W., Weber, E., Kalble, T., Pareckh, N. and Georgi, P. Pharmacokinetics of Technetium-99m-$MAG_3$ in human. J. Nucl. Med. 1990, 31, 1285-1293
  8. Chakravarty, M., Sanyal, S. and Banerjee, S. Technetium-99m amino acid chelates: correlation of their physico-chemical and physiological parameters.part III. J. Inorg. Biochem. 1990, 39, 43-57
  9. Egli, A., Alberto, R., Tannahill, L., Schibli, R., Abram, U., Schaffland, A., Waibel, R., Tourwe, D., Jeannin, L., Iterbeke, K. and Schubiger, P. A. Organometallic $^{99m}Tc$-aquaion labels peptide to an unprecedented high specific activity. J. Nucl. Med. 1999, 40, 1913-1917
  10. Eshima, D., Taylor, A., Fritzberg, Jr. A. R., Kasina, S., Hansen, L. and Sorenson, J. F. Animal evaluation of technetium-99m triamide mercaptide complexes as potential renal imaging agents. J. Nucl. Med. 1987, 28, 1180-1186
  11. Kibar, M., Noyan, A. and Anarat, A. $^{99m}$Tc-N,Nethylenedicysteine scintigraphy in children with various renal disorder: A comparative study with $^{99m}Tc-MAG_3.$/ Nucl. Med. Commun. 1997, 18, 44-52
  12. Morran, J. K. Technetium-99m-EC and other potential new agents in renal nuclear medicine. Semin. Nucl. Med. 1999, 29, 91-101
  13. Reisgys, M., Wust, F., Alberto, R., Schibli, R., Schubiger, P. A., Pietzsch, H. J., Spies, H. and Johannsen, B. Synthesis of rhenium(I) and technetium(I) carbonyl/dithioether ligand complexes bearing 3, 17$\beta$-estradiol. Bioorg. Med. Chem. Lett. 1997, 7, 2243-2246
  14. Taylor, A. Radionuclide renography: a personal approach. Semin. Nucl. Med. 1999, 29, 102-127
  15. Tubis, M., Poshick, E. and Mordyke, R. A. Preparation and use of I-131 labeled sodium iodohippurate in kidney function test. Proc. Soc. Exp. Biol. Med. 1960,63, 497-498
  16. Wang, A. Y. and Liu, R. S. Evaluation of the biodistribution and in vivo biochemistry of $^{99m}Tccysteine and ^{99/99m}Tc$-cysteine complexes- a potential renal imaging agent. Nucl. Med. Biol. 1995, 22, 937-942
  17. Zmbova, B., Djokic, D, Bogdanova, V., Tadzer, I., Ajdinovic, B. and Rastovac, M. Synthesis of paminohippuric acid analog and its labeling by technetium-99m. Appl. Radiat. Isot. 1989, 40, 225-234