title: Assessment of melanoma extent and melanoma metastases invasion using electron paramagnetic resonance and bioluminescence imaging.
abstract: The clinical outcome of melanoma depends on the local and distant spread of the disease at the time of diagnosis, as the estimated 5-year survival rate is about 100% for superficial melanoma diagnosed early, but less than 10% for melanoma that has disseminated to major organs such as lungs. There is a crucial need for new effective methods for the detection and the characterization of melanomas. In the pre-clinical setting, this will help to understand the factors that contribute to the malignancy while the transfer into the clinic will contribute to an early effective treatment of patients. Melanoma lesions can be detected by electron paramagnetic resonance (EPR) using paramagnetic properties of melanin pigments. As part of the development of EPR imaging to characterize melanomas, we evaluated in the present study the usefulness of EPR to report on the extension of lung metastases by comparing the method with bioluminescence imaging using B16 melanoma cells expressing luciferase. B16 melanoma cells were injected subcutaneously or intravenously in C57/BL6 mice. The primary tumors or the lung colonization by melanoma cells was measured after several delay periods to obtain several degrees of invasiveness. The animals were measured in-vivo with bioluminescence after i.v. injection of luciferin. The primary tumors or lungs were then excised. After freeze-drying, the content of melanin in lungs was measured and imaged by EPR at 9 GHz. We observed a direct relationship between the EPR intensity and the bioluminescence intensity. Another tumor model (KHT sarcoma), non-pigmented but expressing luciferase, was used to confirm that the EPR signal was directly linked to the melanin pigment present in the tumors.
authors.affiliation: Louvain Drug Research Institute, Biomedical Magnetic Resonance Research Group, Université Catholique de Louvain, Avenue Mounier 73, B-1200 Brussels, Belgium.
authors.forename: Quentin
authors.initials: Q
authors.lastname: Godechal
authors.forename: Florence
authors.initials: F
authors.lastname: Defresne
authors.forename: Pierre
authors.initials: P
authors.lastname: Danhier
authors.forename: Philippe
authors.initials: P
authors.lastname: Leveque
authors.forename: Paolo Ettore
authors.initials: PE
authors.lastname: Porporato
authors.forename: Pierre
authors.initials: P
authors.lastname: Sonveaux
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Baurain
authors.forename: Olivier
authors.initials: O
authors.lastname: Feron
authors.forename: Bernard
authors.initials: B
authors.lastname: Gallez
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004578:Electron Spin Resonance Spectroscopy / Q000379:methods*; D006801:Humans; D008297:Male; D008543:Melanins / Q000378:metabolism; D008545:Melanoma / Q000175:diagnosis* / Q000378:metabolism; D008546:Melanoma, Experimental; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D008543:Melanins