CNR ExploRA

Articolo in rivista, 2014, ENG, 10.1007/s11307-013-0669-0

Validation of an Engineered Cell Model for In Vitro and In Vivo HIF-1? Evaluation by Different Imaging Modalities

Alessia Lo Dico 1,2,3; Silvia Valtorta 4,5,6; C. Martelli 2,7; Sara Belloli 4,5,6; U. Gianelli 1,8; D. Tosi 7; S. Bosari 1,2,8; A. Degrassi 9; M. Russo 9; Isabella Raccagni 4,5,6,10; Giovanni Lucignani 2,7,11; Rosa Maria Moresco 4,5,6; Luisa Ottobrini 1,2,6

1. Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy. 2. Centre of Molecular and Cellular Imaging-IMAGO, Milan, Italy. 3. Doctorate School of Molecular Medicine, University of Milan, Milan, Italy. 4. Tecnomed Foundation and Department of Health Sciences, University of Milan-Bicocca, Milan, Italy. 5.Department of Nuclear Medicine, San Raffaele Scientific Institute, Milan, Italy. 6. Institute for Molecular Bioimaging and Physiology (IBFM), National Research Council (CNR), Milan, Italy. 7. Department of Health Sciences, University of Milan, Milan, Italy. 8. Pathology Unit, IRCCS Ca Granda-Ospedale Maggiore Policlinico Foundation, Milan, Italy. 9. Nerviano Medical Sciences, Nerviano, MI, Italy 10. Doctorate in Biomedical Technologies, University of Milan-Bicocca, Milan, Italy. 11. Department of Diagnostic Services, Unit of Nuclear Medicine, San Paolo Hospital, Milan, Italy.

PURPOSE: The aim of this study was to characterize a cell-based model for the molecular study of hypoxia-inducible factor (HIF)-1? activity, in the context of hypoxia, by means of different imaging techniques. PROCEDURES: Engineered U251-HRE glioma cells were used to analyze the molecular mechanisms underlying HIF-1? activity in vitro in relation to luciferase expression. The same cells were orthotopically implanted in mice to evaluate tumor progression and hypoxia induction by bioluminescence imaging, fluorescence imaging, positron emission tomography (PET), and magnetic resonance imaging (MRI). RESULTS: In vitro analyses highlighted the relationship between HIF-1? and luciferase activity in hypoxic conditions and after pharmacological treatments in U251-HRE cells. Through in vivo studies, it was possible to assess hypoxia establishment in relation to tumor growth by optical imaging, PET and MRI. CONCLUSIONS: The findings of this study indicate that the U251-HRE orthotopic murine model can be used to reliably evaluate processes modulating HIF-1? activity, using both molecular and preclinical non-invasive imaging techniques.

Molecular imaging and biology 16 (2), pp. 210–223