TY - JOUR
T1 - Comparison of molecular markers of hypoxia and imaging with 60Cu-ATSM in cancer of the uterine cervix
AU - Grigsby, Perry W.
AU - Malyapa, Robert S.
AU - Higashikubo, Ryuji
AU - Schwarz, Julie K.
AU - Welch, Michael J.
AU - Huettner, Phyllis C.
AU - Dehdashti, Farrokh
N1 - Funding Information:
Acknowledgement. The authors acknowledge Jason Lewis, Ph.D., and the staff who produced the Cu-ATSM. This work is also supported in part by NIH Grant CA086307-08, DOE Grant DE-FG02-87, and *RSNA grant MSD0404.
PY - 2007/9
Y1 - 2007/9
N2 - 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.
AB - 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.
KW - Cervical cancer
KW - Hypoxia-PET imaging
KW - Prognostic markers
UR - http://www.scopus.com/inward/record.url?scp=34548151815&partnerID=8YFLogxK
U2 - 10.1007/s11307-007-0095-2
DO - 10.1007/s11307-007-0095-2
M3 - Article
C2 - 17431727
AN - SCOPUS:34548151815
SN - 1536-1632
VL - 9
SP - 278
EP - 283
JO - Molecular Imaging and Biology
JF - Molecular Imaging and Biology
IS - 5
ER -