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

Abstract

PURPOSE:

To determine if hypoxia-related molecular markers are associated with (60)Cu labeled diacetyl-bis (N4 -methylthiosemicarbazone); ((60)Cu-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 (60)Cu-ATSM. (60)Cu-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 (60)Cu-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 (60)Cu-ATSM to be a significant independent predictor of tumor recurrence (p = 0.0287).

CONCLUSIONS:

(60)Cu-ATSM hypoxia was correlated with overexpression of VEGF, EGFR, COX-2, CA-9, an increase in apoptosis, and a poor outcome.

• Authors: Perry W Grigsby, Robert S Malyapa, Ryuji Higashikubo, Julie K Schwarz, Michael J Welch, Phyllis C Huettner, Farrokh Dehdashti
• Journal: Molecular imaging and biology (Mol Imaging Biol) 2007 Sep-Oct Vol. 9 Issue 5 Pg. 278-83 ISSN: 1536-1632 [Print] United States
• PMID: 17431727 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Biomarkers
• Biomarkers, Tumor
• Coordination Complexes
• Copper Radioisotopes
• Organometallic Compounds
• Radiopharmaceuticals
• Thiosemicarbazones
• VEGFA protein, human
• Vascular Endothelial Growth Factor A
• copper (II) diacetyl-di(N(4)-methylthiosemicarbazone)
• Cyclooxygenase 2
• PTGS2 protein, human
• ErbB Receptors

Topics

• Adult
• Aged
• Aged, 80 and over
• Biomarkers (metabolism)
• Biomarkers, Tumor (metabolism)
• Coordination Complexes
• Copper Radioisotopes
• Cyclooxygenase 2 (metabolism)
• ErbB Receptors (metabolism)
• Female
• Humans
• Hypoxia (diagnostic imaging, metabolism)
• Middle Aged
• Neovascularization, Pathologic
• Organometallic Compounds
• Pilot Projects
• Prospective Studies
• Radionuclide Imaging
• Radiopharmaceuticals
• Thiosemicarbazones
• Uterine Cervical Neoplasms (blood supply, diagnostic imaging, metabolism)
• Vascular Endothelial Growth Factor A (metabolism)