Skip to main content
SpringerLink
Log in

Evaluation of62Cu labeled diacetyl-bis(N 4-methylthiosemicarbazone) as a hypoxic tissue tracer in patients with lung cancer

  • Original Articles
  • Published:
Annals of Nuclear Medicine Aims and scope Submit manuscript

Abstract

62Cu labeled diacetyl-bis(N4-methylthiosemicarbazone) (62Cu-ATSM) has been proposed as a generator-produced, positron-emitting tracer for hypoxic tissue imaging. From basic studies, the retention mechanism of62Cu-ATSM is considered to be closely related to cytosolic/microsomal bioreduction, a possible system for hypoxic bioreductive drug activation. In order to evaluate the characteristics of62Cu-ATSM, PET studies were performed in 4 normal subjects and 6 patients with lung cancer.62Cu-ATSM cleared rapidly from the blood with little lung uptake (0.43±0.09, uptake ratio; divided by the arterial input function) in normal subjects. Intense tumor uptake of62Cu-ATSM was observed in all patients with lung cancer (3.00±1.50). A negative correlation was observed between blood flow and flow-normalized62Cu-ATSM uptake in three of four patients. In contrast,62Cu-ATSM uptake was not related to that of18F-fluorodeoxyglucose. The negative correlation between blood flow and flow normalized62Cu-ATSM uptake suggests an enhancement of retention of62Cu-ATSM by low flow.62Cu-ATSM is a promising PET tracer for tumor imaging, which might bring new information for chemotherapeutic treatment as well as radiotherapy of hypoxic tumors.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Coleman CN. Hypoxia in tumors: A paradigm for the approach to biochemical and physiological heterogeneity.J Natl Cancer Inst 80: 310–317, 1998.

    Article  Google Scholar 

  2. Teicher BA, Lazo JS, Sartorelli AC. Classification of antineoplastic agents by their selective toxicities toward oxygenated and hypoxic tumor cells.Cancer Res 41(1): 73–81, 1981.

    PubMed  CAS  Google Scholar 

  3. Chapman JD, Baer K, Lee J. Characteristics of the metabolism-induced binding of misonidazole to hypoxic mammalian cells.Cancer Res 43: 1523–1528, 1983.

    PubMed  CAS  Google Scholar 

  4. Jerabek PA, Patrick TB, Kilbourn MR, Dischino DD, Welch MJ. Synthesis and biodistribution of18F-labeled fluoromisonidazoles: potentialin vivo markers of hypoxic tissue.Int J Radiate App Instrum [A] 37: 599–605, 1986.

    Article  CAS  Google Scholar 

  5. Mannan RH, Somayaji VV, Lee J, Mercer JR, Chapman JD, Wiebe LI. Radiolabeled 1-(5-iodo-5-deoxy-β-d-arabinofuranosyl)-2-nitroimidazole (iodoazomycin arabinoside: IAZA): a novel marker of tissue hypoxia.J Nucl Med 32: 1764–1770, 1991.

    PubMed  CAS  Google Scholar 

  6. Linder KE, Chan YW, Cyr JE, Malley MF, Nowotnik DP, Nunn AD. Technetium-O(PnAO-(2-nitroimidazole)) [BMS181321], a new technetium-containing nitroimidazole complex for imaging hypoxia: synthesis characterization and xanthine oxidase-catalyzed reduction.J Med Chem 37: 9–17, 1994.

    Article  PubMed  CAS  Google Scholar 

  7. Koh WJ, Rasey JS, Evans ML, Grierson JR, Lewellen TK, Graham MM, et al. Imaging of hypoxia in human tumors with [F-18]fluoromisonidazole.Int J Radiate Once Biol Phys 22: 199–212, 1992.

    Article  CAS  Google Scholar 

  8. Fujibayashi Y, Taniuchi H, Yonekura Y, Ohtani H, Konishi J, Yokoyama A. Copper-62-ATSM: a new hypoxia imaging agent with high membrane permeability and low redox potential.J Nucl Med 38: 1155–1160, 1997.

    PubMed  CAS  Google Scholar 

  9. Fujibayashi Y, Taniuchi H, Wada A, Yonekura Y, Konishi J, Yokoyama A. Differential mechanism of retention of Cupyruvaldehyde-bis(N 4-methylthiosemicarbazone) (Cu-PTSM) by brain and tumor: a novel radiopharmaceutical for positron emission tomography imaging.Ann Nucl Med 9: 1–5, 1995.

    PubMed  CAS  Google Scholar 

  10. Wada K, Fujibayashi Y, Tajima N, Yokoyama A. Cu-ATSM, an intracellular-accessible superoxide dismutase (SOD)-like copper complex: evaluation in an ischemia-reperfusion injury model.Biol Pharm Bull 17: 701–704, 1994.

    PubMed  CAS  Google Scholar 

  11. Lewis JS, McCarthy DW, McCarthy TJ, Fujibayashi Y, Welch MJ. Evaluation of64Cu-ATSMin vitro andin vivo in a hypoxic tumor model.J Nucl Med 40: 177–183, 1999.

    PubMed  CAS  Google Scholar 

  12. Matsumoto K, Fujibayashi Y, Yonekura Y. Application of the new zinc-62/copper-62 generator: an effective labeling method for62Cu-PTSM.Nucl Med Biol 19: 39–44, 1992.

    CAS  Google Scholar 

  13. Gingas BA, Suprunchuk T, Bayley CH. The preparation of some thiosemicarbazones and their copper complexes. Part III.Can J Chem 40: 1053–1059, 1962.

    Article  Google Scholar 

  14. DeGrado TR, Turkington, TG, Williams JJ, Stearns CW, Hoffman JM, Coleman RE. Performance characteristics of a whole-body PET scanner.J Nucl Med 35: 1398–1406. 1994.

    PubMed  CAS  Google Scholar 

  15. Herscovitch P, Markham J, Raichle ME. Brain blood flow measured with intravenous H2 16O. I. theory and error analysis.J Nucl Med 24: 782–789, 1983.

    PubMed  CAS  Google Scholar 

  16. Raichle ME, Martin WRW, Herscovitch P, Mintun MA, Markham J. Brain blood flow measured with intravenous H2 15O. II. implementation and validation.J Nucl Med 24: 790–798, 1983.

    PubMed  CAS  Google Scholar 

  17. Meyer E. Simultaneous correction for tracer arrival delay and dispersion in CBF measurements by the H2 15O autoradiographic method and dynamic PET.J Nucl Med 30: 1069–1078, 1989.

    PubMed  CAS  Google Scholar 

  18. Fujibayashi Y, Yoshimi E, Waki A, Takahashi N, Yonekura Y. Cu-ATSM, a new tumor agent predicting ability for bioreductive drug activation.J Nucl Med 39 (suppl): 90P, 1998. [abstract]

Download references

Author information

Authors and Affiliations

  1. Department of Radiology, Fukui Medical University, Shimoaizuki, Matsuokacho, Yoshida-gun, 910-1137, Fukui, Japan

    Norio Takahashi, Tatsuro Tsuchida, Katsuya Sugimoto & Harumi Itoh

  2. Biomedical Imaging Research Center, Fukui Medical University, Shimoaizuki, Matsuokacho, Yoshida-gun, 910-1137, Fukui, Japan

    Yasuhisa Fujibayashi, Yoshiharu Yonekura, Atsuo Waki & Norihiro Sadato

  3. Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO, USA

    Michael J. Welch

Authors
  1. Norio Takahashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yasuhisa Fujibayashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yoshiharu Yonekura
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Michael J. Welch
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Atsuo Waki
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Tatsuro Tsuchida
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Norihiro Sadato
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Katsuya Sugimoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Harumi Itoh
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Tatsuro Tsuchida.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Takahashi, N., Fujibayashi, Y., Yonekura, Y. et al. Evaluation of62Cu labeled diacetyl-bis(N 4-methylthiosemicarbazone) as a hypoxic tissue tracer in patients with lung cancer. Ann Nucl Med 14, 323–328 (2000). https://doi.org/10.1007/BF02988690

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02988690

Key words

Search

Navigation