Advertisement

Annals of Nuclear Medicine

, Volume 14, Issue 5, pp 323–328 | Cite as

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

  • Norio Takahashi
  • Yasuhisa Fujibayashi
  • Yoshiharu Yonekura
  • Michael J. Welch
  • Atsuo Waki
  • Tatsuro TsuchidaEmail author
  • Norihiro Sadato
  • Katsuya Sugimoto
  • Harumi Itoh
Original Articles

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.

Key words

62Cu-ATSM hypoxia lung cancer 18F-FDG PET 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Coleman CN. Hypoxia in tumors: A paradigm for the approach to biochemical and physiological heterogeneity.J Natl Cancer Inst 80: 310–317, 1998.CrossRefGoogle Scholar
  2. 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.PubMedGoogle Scholar
  3. 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.PubMedGoogle Scholar
  4. 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.CrossRefGoogle Scholar
  5. 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.PubMedGoogle Scholar
  6. 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.PubMedCrossRefGoogle Scholar
  7. 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.CrossRefGoogle Scholar
  8. 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.PubMedGoogle Scholar
  9. 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.PubMedGoogle Scholar
  10. 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.PubMedGoogle Scholar
  11. 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.PubMedGoogle Scholar
  12. 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.Google Scholar
  13. 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.CrossRefGoogle Scholar
  14. 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.PubMedGoogle Scholar
  15. 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.PubMedGoogle Scholar
  16. 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.PubMedGoogle Scholar
  17. 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.PubMedGoogle Scholar
  18. 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]Google Scholar

Copyright information

© Springer 2000

Authors and Affiliations

  • Norio Takahashi
    • 1
  • Yasuhisa Fujibayashi
    • 2
  • Yoshiharu Yonekura
    • 2
  • Michael J. Welch
    • 3
  • Atsuo Waki
    • 2
  • Tatsuro Tsuchida
    • 1
    Email author
  • Norihiro Sadato
    • 2
  • Katsuya Sugimoto
    • 1
  • Harumi Itoh
    • 1
  1. 1.Department of RadiologyFukui Medical UniversityFukuiJapan
  2. 2.Biomedical Imaging Research CenterFukui Medical UniversityFukuiJapan
  3. 3.Mallinckrodt Institute of RadiologyWashington University School of MedicineSt. LouisUSA

Personalised recommendations