Identification of imaging biomarkers for the assessment of tumour response to different treatments in a preclinical glioma model
Articolo
Data di Pubblicazione:
2015
Citazione:
Identification of imaging biomarkers for the assessment of tumour response to different treatments in a preclinical glioma model / A. Lo Dico, C. Martelli, S. Valtorta, I. Raccagni, C. Diceglie, S. Belloli, U. Gianelli, V. Vaira, L.S. Politi, S. Bosari, G. Lucignani, R.M. Moresco, L. Ottobrini. - In: EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING. - ISSN 1619-7070. - 42:7(2015 Jun), pp. 1093-1105. [10.1007/s00259-015-3040-7]
Abstract:
PURPOSE:
Hypoxia-inducible factor 1α (HIF-1α) activity is one of the major players in hypoxia-mediated glioma progression and resistance to therapies, and therefore the focus of this study was the evaluation of HIF-1α modulation in relation to tumour response with the purpose of identifying imaging biomarkers able to document tumour response to treatment in a murine glioma model.
METHODS:
U251-HRE-mCherry cells expressing Luciferase under the control of a hypoxia responsive element (HRE) and mCherry under the control of a constitutive promoter were used to assess HIF-1α activity and cell survival after treatment, both in vitro and in vivo, by optical, MRI and positron emission tomography imaging.
RESULTS:
This cell model can be used to monitor HIF-1α activity after treatment with different drugs modulating transduction pathways involved in its regulation. After temozolomide (TMZ) treatment, HIF-1α activity is early reduced, preceding cell cytotoxicity. Optical imaging allowed monitoring of this process in vivo, and carbonic anhydrase IX (CAIX) expression was identified as a translatable non-invasive biomarker with potential clinical significance. A preliminary in vitro evaluation showed that reduction of HIF-1α activity after TMZ treatment was comparable to the effect of an Hsp90 inhibitor, opening the way for further elucidation of its mechanism of action.
CONCLUSION:
The results of this study suggest that the U251-HRE-mCherry cell model can be used for the monitoring of HIF-1α activity through luciferase and CAIX expression. These cells can become a useful tool for the assessment and improvement of new targeted tracers for potential theranostic procedures.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
Biomarker; CAIX; HIF-1alpha; Optical imaging; Temozolomide
Elenco autori:
A. Lo Dico, C. Martelli, S. Valtorta, I. Raccagni, C. Diceglie, S. Belloli, U. Gianelli, V. Vaira, L.S. Politi, S. Bosari, G. Lucignani, R.M. Moresco, L. Ottobrini
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