Prognostic significance of hypoxic PET using (18)F-FAZA and (62)Cu-ATSM in non-small-cell lung cancer.

Abstract

OBJECTIVES:

Tumor hypoxia is believed to have a strong correlation with the resistance to chemoradiotherapy. Noninvasive evaluation of hypoxic status in tumors using molecular imaging has the potential to characterize the tumor aggressiveness. We evaluated the clinical usefulness of newly-developed tumor hypoxic positron emission tomography (PET) tracers in localized non-small-cell lung cancer (NSCLC).

PATIENTS AND METHODS:

Forty-seven patients with localized NSCLC received either or both hypoxic PETs using the tracers: (18)F-fluoroazomycin arabinoside ((18)F-FAZA) (n=45) and/or (62)Cu-diacetyl-bis (N4)-methylsemithiocarbazone ((62)Cu-ATSM) (n=22). All received (18)F-fluorodeoxyglucose ((18)F-FDG) PET tracer (n=47). We examined the correlation between uptake of three PET tracers and clinicopathological factors, and evaluated their impacts on survival after treatment retrospectively.

RESULTS:

A couple of commonly-identified unfavorable factors such as presence of vascular invasion and pleural invasion was significantly correlated with higher uptake of these hypoxic agents as well as that of (18)F-FDG. Larger tumor diameter, high neutrophil-to-lymphocyte ratio and advanced pathological stage were also associated with accumulation of hypoxic PETs ((18)F-FAZA, p<0.01; (62)Cu-ATSM, p<0.04), but not with that of (18)F-FDG. The patients with a higher accumulation had significantly poorer overall survival [(18)F-FAZA, HR (hazard ratio), 9.50, p<0.01; (62)Cu-ATSM, HR, 4.06, p<0.05] and progression free survival ((18)F-FAZA, HR, 5.28, p<0.01, (62)Cu-ATSM, HR, 2.72, p<0.05).

CONCLUSION:

Both (18)F-FAZA and (62)Cu-ATSM PET provide useful information regarding tumor aggressiveness and prediction of survival among NSCLC patients. We believe these hypoxic PETs could contribute to the establishment of the optimally individualized treatment of NSCLC.

• Authors: Tomonari Kinoshita, Hirofumi Fujii, Yuichiro Hayashi, Ikuo Kamiyama, Takashi Ohtsuka, Hisao Asamura
• Journal: Lung cancer (Amsterdam, Netherlands) (Lung Cancer) Vol. 91 Pg. 56-66 (Jan 2016) ISSN: 1872-8332 [Electronic] Ireland
• PMID: 26711935 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Coordination Complexes
• Nitroimidazoles
• Organometallic Compounds
• Radiopharmaceuticals
• Thiosemicarbazones
• copper (II) diacetyl-di(N(4)-methylthiosemicarbazone)
• Fluorodeoxyglucose F18
• fluoroazomycin arabinoside

Topics

• Aged
• Aged, 80 and over
• Carcinoma, Non-Small-Cell Lung (diagnostic imaging, drug therapy, pathology, radiotherapy)
• Cell Hypoxia (physiology)
• Coordination Complexes
• Drug Resistance, Neoplasm
• Female
• Fluorodeoxyglucose F18 (analysis)
• Humans
• Lung Neoplasms (diagnostic imaging, drug therapy, pathology, radiotherapy)
• Male
• Middle Aged
• Nitroimidazoles (analysis)
• Organometallic Compounds (analysis)
• Positron-Emission Tomography (methods)
• Prognosis
• Radiopharmaceuticals (analysis)
• Retrospective Studies
• Survival Analysis
• Thiosemicarbazones (analysis)