Comparison of molecular markers of hypoxia and imaging with 60Cu-ATSM in cancer of the uterine cervix

Perry W. Grigsby, Robert S. Malyapa, Ryuji Higashikubo, Julie K. Schwarz, Michael J. Welch, Phyllis C. Huettner, Farrokh Dehdashti

Research output: Contribution to journalArticle

70 Scopus citations

Abstract

Purpose: To determine if hypoxia-related molecular markers are associated with 60Cu labeled diacetyl-bis (N4-methylthiosemicarbazone); (60Cu-ATSM) imaging of tumor hypoxia in cervical cancer. Procedures: Fifteen patients were enrolled in a prospective study and underwent evaluation of tumor hypoxia with positron emission tomography (PET) using 60Cu-ATSM. 60Cu-ATSM-PET imaging was compared with the expression of tissue molecular markers, which included vascular endothelial growth factor (VEGF), cyclo-oxygenase-2 (COX-2), epidermal growth factor receptor (EGFR), carbonic anyhdrase IX (CA-9), and apoptotic index. Results: Six patients had hypoxic tumors determined by 60Cu-ATSM, and nine had non-hypoxic tumors. The 4-year overall survival estimates were 75% for patients with non-hypoxic tumors and 33% for those with hypoxic tumors (p=0.04). Overexpression of VEGF (p=0.13), EGFR (p=0.05), CA-9 (p=0.02), COX-2 (p=0.08), and the presence of apoptosis (p=0.005) occurred in patients with hypoxic tumors. Cox proportional hazards modeling demonstrated hypoxia as determined by 60Cu-ATSM to be a significant independent predictor of tumor recurrence (p=0.0287). Conclusions: 60Cu-ATSM hypoxia was correlated with overexpression of VEGF, EGFR, COX-2, CA-9, an increase in apoptosis, and a poor outcome.

Original languageEnglish
Pages (from-to)278-283
Number of pages6
JournalMolecular Imaging and Biology
Volume9
Issue number5
DOIs
StatePublished - Sep 1 2007

Keywords

  • Cervical cancer
  • Hypoxia-PET imaging
  • Prognostic markers

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