In vivo assessment of tumor hypoxia in lung cancer with 60Cu-ATSM

Eur J Nucl Med Mol Imaging. 2003 Jun;30(6):844-50. doi: 10.1007/s00259-003-1130-4. Epub 2003 Apr 12.

Abstract

Tumor hypoxia is recognized as an important determinant of response to therapy. In this study we investigated the feasibility of clinical imaging with copper-60 diacetyl-bis( N(4)-methylthiosemicarbazone) ((60)Cu-ATSM) in patients with non-small-cell lung cancer (NSCLC) and also assessed whether pretreatment tumor uptake of (60)Cu-ATSM predicts tumor responsiveness to therapy. Nineteen patients with biopsy-proved NSCLC were studied by positron emission tomography (PET) with (60)Cu-ATSM before initiation of therapy. (60)Cu-ATSM uptake was evaluated semiquantitatively by determining the tumor-to-muscle activity ratio (T/M). All patients also underwent PET with fluorine-18 fluorodeoxyglucose (FDG) prior to institution of therapy. The PET results were correlated with follow-up evaluation (2-46 months). It was demonstrated that PET imaging with (60)Cu-ATSM in patients with NCSLC is feasible. The tumor of one patient had no discernible (60)Cu-ATSM uptake, whereas the tumor uptake in the remaining patients was variable, as expected. Response was evaluated in 14 patients; the mean T/M for (60)Cu-ATSM was significantly lower in responders (1.5+/-0.4) than in nonresponders (3.4+/-0.8) (P=0.002). However, the mean SUV for (60)Cu-ATSM was not significantly different in responders (2.8+/-1.1) and nonresponders (3.5+/-1.0) ( P=0.2). An arbitrarily selected T/M threshold of 3.0 discriminated those likely to respond to therapy: all eight responders had a T/M <3.0 and all six nonresponders had a T/M > or =3.0. Tumor SUV for FDG was not significantly different in responders and nonresponders (P=0.7) and did not correlate with (60)Cu-ATSM uptake (r=0.04; P=0.9). (60)Cu-ATSM-PET can be readily performed in patients with NSCLC and the tumor uptake of (60)Cu-ATSM reveals clinically unique information about tumor oxygenation that is predictive of tumor response to therapy.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biological Transport
  • Cell Hypoxia / physiology*
  • Copper Radioisotopes* / pharmacokinetics
  • Female
  • Humans
  • Lung Neoplasms / diagnostic imaging*
  • Lung Neoplasms / pathology
  • Lung Neoplasms / therapy
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Organometallic Compounds / pharmacokinetics
  • Organometallic Compounds / therapeutic use*
  • Phantoms, Imaging
  • Predictive Value of Tests
  • Radiopharmaceuticals / pharmacokinetics
  • Thiosemicarbazones / pharmacokinetics
  • Thiosemicarbazones / therapeutic use*
  • Tomography, Emission-Computed
  • Tomography, X-Ray Computed
  • Treatment Outcome

Substances

  • Copper Radioisotopes
  • Organometallic Compounds
  • Radiopharmaceuticals
  • Thiosemicarbazones
  • copper (II) diacetyl-di(N(4)-methylthiosemicarbazone)