Journal of Nuclear Science, Engineering and Technology (JONSAT)
In cooperation with the Iranian Nuclear Society

Preparation of [61Cu]Bleomycin Complex as a Potenlial PET Radiopharmaceutical and it’s Biological Evaluation in Normal and Tumor-Bearing Rodents

Editorial

Authors

A.R Jalilian
H Zandi
M Akhlaghi
M Kamali Dehghan
F Bolourinovin
S Moradkhani
A Majdabadi
Abstract
[61Cu]Bleomycin ([61Cu]BLM) was prepared using [61Cu]CuCl2 produced via natZn(p,x)61Cu (180μA proton irradiation, 22MeV, 3.2h), purified by ion chromatography method. [61Cu]BLM was prepared at optimized conditions (room temperature, 45 min, 0.1 mg bleomycin for 2-10mCi 61CuCl2) with radiochemical purity over 98% determined by HPLC and RTLC. [61Cu]BLM was administered into the normal and tumor bearing rodents up to 210 minutes followed by biodistribution and co incidence imaging studies. A significant tumor/non tumor accumulation was observed either by animal sacrification or imaging method. [61Cu]BLM can be a potential PET radiotracer for tumor imaging.

Highlights

 

 

  1. 1.    D.W. McCarthy, L.A. Bass, P.D. Cutler, R.E. Shefer, R.E. Klinkowstein, P. Herrero, J.S. Lewis, C.S. Cutler, C.J. Anderson, M.J. Welch, “High purity production and potential applications of copper-60 and copper-61,” Nucl. Med. Biol. 26;4: 351-358 (1999).

 

  1. 2.    T. Fukumura, K. Okada, F. Szelecsényi, Z. Kovács, K. Suzuki, “Practical production of 61Cu using natural Co target and its simple purification with a chelating resin,” Radiochimica Acta; 92, 209-214 ( 2004).

 

  1. 3.    J.S. Lewis, T.L. Sharp, R. Laforest, Y. Fujibayashi, M.J. Welch, “Tumor uptake of copper-diacetyl-bis (N4-Methylthiosemicarbazone): effect of changes in tissue oxygenation,” J. Nucl. Med. 42, 655-661 (2001).

 

  1. 4.    A.R. Jalilian, P. Rowshanfarzad, M. Sabet, A. Shafiee, “Preparation of [61Cu]-2-acetylpyridine thiosemicarbazone complex as a possible PET tracer for malignancies,” Applied Radiat. Isotopes, 64, 337-341 (2006).

 

  1. 5.    S.T. Hoehn, H.D. Junker, R.C. Bunt, C.J. Turner, J. Stubbe, “Solution structure of Co(III)-Bleomycin-OOH bound to a phosphoglycolate lesion containing oligonucleotide: implications for bleomycin-induced double-strand DNA cleavage,” Biochemistry, 22, 5894-5905 (2001).

 

  1. 6.    T. Korppi-Tommola, H. Huhmar, H.J. Aronen, “111In-Labelled bleomycin complex for the differentiation of high- and low-grade gliomas,” Nucl. Med. Commun. 20, 145-152 (1999).

 

  1. 7.    H.A. Jaaskela-Saari, K.J. Kairemo, H.A. Ramsay, R. Grenman, “Labelling of bleomycin with auger-emitter increases cytotoxicity in squamous-cell cancer cell lines,” Intl. J. Radiat. Biol. 73, 565-570 (1998).

 

  1. 8.    P.H. Stern, S.E. Halpern, P.L. Hagan, S.B. Howell, J.E. Dabbs, R.M. Gordon, “Cytotoxic activity, tumor accumulation and tissue distribution of ruthenium-103-labeled-bleomycin,” J. Nat. Cancer. Inst. 64, 807-811 (1981).

 

  1. 9.    R.C. Brooks, P. Carnochan, J.F. Vollano, Z. Powell, J.K. Sasabowski, S. Martellucci, M.C. Darkes, S.P. Fricker, B.A. Murrer, “Metal complexes of bleomycin: evaluation [Rh-105]-Bleomycin for use in targeted radiotherapy,” Nucl. Med. Biol. 26, 421-430 (1999).

 

10. P. Rowshanfarzad, M. Sabet, A.R. Jalilian, M. Kamalidehghan, “An overview of copper radionuclides and production of 61Cu by proton irradiation of natZn at a medical cyclotron,” Applied Radiat. Isotopes, 64, 1563–1573 (2006).

11. M. Blann, J. Bislinghoff, “Code Alice/Livermore 91, lawrence livermore national laboratory,” Internal Report, UCID-19614 (1991).

 

12. J.F. Ziegler, J.P. Biersack, U. Littmark, “The code of SRIM- the stopping and range of ions in matter,” Version 2000. X (2000).

 

13. A.M. Weisberg, “Gold plating,” 9th Ed, ASM International, 247, U.S.A (1990).

 

14. R. Schwarzbach, K. Zimmerman, P. Bläuenstein, A. Smith, P.A. Schubiger, “Development of a simple and selective separation of 67Cu from irradiated zinc for use in antibody labelling: a comparison of methods,” Appl. Radiat Isot. 46, 329-335 (1995).

 

15. Z. Marczenko, “In: spectrophotometric determination of elements,” 4th Ed, John Wiley & Sons Inc, 281, New York (1976).

 

16. Z. Marczenko, “In: spectrophotometric determination of elements,” 4th Ed, John Wiley & Sons Inc, 601, New York (1976).

 

17. D.L. Melnyk, S.B. Horwitz, J. Peisach, “The oxidation-reduction potential of copper-bleomycin,” Inorganica Chimica Acta, 138, 75-78 (1987).

 

18. W.E. Antholine, D. Solaiman, L.A. Saryan, D.H. Petering, “Studies on the chemical reactivity of copper bleomycin,” J. Inorganic Biochem. 11, 7544-47 (1982).

 

19. Y. Litaka, H. Nakamura, T. Nakatani, “Optical spectrometric properties of copper-bleomycin,” J. Antibiotics, 31, 1973-1975 (1978).

 

20. R.D. Bereman, M.E. Winkler, “A spectral investigation of the copper complex of the antitumor compound bleomycin,” J. Inorg. Biochem. 13, 95-104 (1980).

 

21. A.D. Nunn, J. Lunec, “A comparison of the effect of metal-bleomycin complexes on the DNA damage and survival of cultured mammalian cells,” Eur. J. Cancer. 14, 857-863 (1978).

 

22. Martindale, The Extra Pharmacopoeia, “Bleomycin monograph,” 31st. Ed. Vo. 1, 546-547 (1996).

 

23. Welwyn, Herts, “Proceedings of First International Symposium on Bleomycin,” (1973), London, Lundbeck Ltd, 34 (1972).

Keywords

Radiopharmaceutical
Copper-61
Bleomycin
Positron Emission Tomography
Radiolabeling
Quality Control

  1.  

     

    1. 1.    D.W. McCarthy, L.A. Bass, P.D. Cutler, R.E. Shefer, R.E. Klinkowstein, P. Herrero, J.S. Lewis, C.S. Cutler, C.J. Anderson, M.J. Welch, “High purity production and potential applications of copper-60 and copper-61,” Nucl. Med. Biol. 26;4: 351-358 (1999).

     

    1. 2.    T. Fukumura, K. Okada, F. Szelecsényi, Z. Kovács, K. Suzuki, “Practical production of 61Cu using natural Co target and its simple purification with a chelating resin,” Radiochimica Acta; 92, 209-214 ( 2004).

     

    1. 3.    J.S. Lewis, T.L. Sharp, R. Laforest, Y. Fujibayashi, M.J. Welch, “Tumor uptake of copper-diacetyl-bis (N4-Methylthiosemicarbazone): effect of changes in tissue oxygenation,” J. Nucl. Med. 42, 655-661 (2001).

     

    1. 4.    A.R. Jalilian, P. Rowshanfarzad, M. Sabet, A. Shafiee, “Preparation of [61Cu]-2-acetylpyridine thiosemicarbazone complex as a possible PET tracer for malignancies,” Applied Radiat. Isotopes, 64, 337-341 (2006).

     

    1. 5.    S.T. Hoehn, H.D. Junker, R.C. Bunt, C.J. Turner, J. Stubbe, “Solution structure of Co(III)-Bleomycin-OOH bound to a phosphoglycolate lesion containing oligonucleotide: implications for bleomycin-induced double-strand DNA cleavage,” Biochemistry, 22, 5894-5905 (2001).

     

    1. 6.    T. Korppi-Tommola, H. Huhmar, H.J. Aronen, “111In-Labelled bleomycin complex for the differentiation of high- and low-grade gliomas,” Nucl. Med. Commun. 20, 145-152 (1999).

     

    1. 7.    H.A. Jaaskela-Saari, K.J. Kairemo, H.A. Ramsay, R. Grenman, “Labelling of bleomycin with auger-emitter increases cytotoxicity in squamous-cell cancer cell lines,” Intl. J. Radiat. Biol. 73, 565-570 (1998).

     

    1. 8.    P.H. Stern, S.E. Halpern, P.L. Hagan, S.B. Howell, J.E. Dabbs, R.M. Gordon, “Cytotoxic activity, tumor accumulation and tissue distribution of ruthenium-103-labeled-bleomycin,” J. Nat. Cancer. Inst. 64, 807-811 (1981).

     

    1. 9.    R.C. Brooks, P. Carnochan, J.F. Vollano, Z. Powell, J.K. Sasabowski, S. Martellucci, M.C. Darkes, S.P. Fricker, B.A. Murrer, “Metal complexes of bleomycin: evaluation [Rh-105]-Bleomycin for use in targeted radiotherapy,” Nucl. Med. Biol. 26, 421-430 (1999).

     

    10. P. Rowshanfarzad, M. Sabet, A.R. Jalilian, M. Kamalidehghan, “An overview of copper radionuclides and production of 61Cu by proton irradiation of natZn at a medical cyclotron,” Applied Radiat. Isotopes, 64, 1563–1573 (2006).

    11. M. Blann, J. Bislinghoff, “Code Alice/Livermore 91, lawrence livermore national laboratory,” Internal Report, UCID-19614 (1991).

     

    12. J.F. Ziegler, J.P. Biersack, U. Littmark, “The code of SRIM- the stopping and range of ions in matter,” Version 2000. X (2000).

     

    13. A.M. Weisberg, “Gold plating,” 9th Ed, ASM International, 247, U.S.A (1990).

     

    14. R. Schwarzbach, K. Zimmerman, P. Bläuenstein, A. Smith, P.A. Schubiger, “Development of a simple and selective separation of 67Cu from irradiated zinc for use in antibody labelling: a comparison of methods,” Appl. Radiat Isot. 46, 329-335 (1995).

     

    15. Z. Marczenko, “In: spectrophotometric determination of elements,” 4th Ed, John Wiley & Sons Inc, 281, New York (1976).

     

    16. Z. Marczenko, “In: spectrophotometric determination of elements,” 4th Ed, John Wiley & Sons Inc, 601, New York (1976).

     

    17. D.L. Melnyk, S.B. Horwitz, J. Peisach, “The oxidation-reduction potential of copper-bleomycin,” Inorganica Chimica Acta, 138, 75-78 (1987).

     

    18. W.E. Antholine, D. Solaiman, L.A. Saryan, D.H. Petering, “Studies on the chemical reactivity of copper bleomycin,” J. Inorganic Biochem. 11, 7544-47 (1982).

     

    19. Y. Litaka, H. Nakamura, T. Nakatani, “Optical spectrometric properties of copper-bleomycin,” J. Antibiotics, 31, 1973-1975 (1978).

     

    20. R.D. Bereman, M.E. Winkler, “A spectral investigation of the copper complex of the antitumor compound bleomycin,” J. Inorg. Biochem. 13, 95-104 (1980).

     

    21. A.D. Nunn, J. Lunec, “A comparison of the effect of metal-bleomycin complexes on the DNA damage and survival of cultured mammalian cells,” Eur. J. Cancer. 14, 857-863 (1978).

     

    22. Martindale, The Extra Pharmacopoeia, “Bleomycin monograph,” 31st. Ed. Vo. 1, 546-547 (1996).

     

    23. Welwyn, Herts, “Proceedings of First International Symposium on Bleomycin,” (1973), London, Lundbeck Ltd, 34 (1972).

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