Molecular electron paramagnetic resonance imaging of melanin in melanomas: a proof‐of‐concept

Abstract

The incidence of malignant melanoma is increasing at an alarming rate. As the clinical outcome of the disease strongly depends on the localization of the lesion, early detection at the initial stages of development is critical. Here, we suggest spatial characterization of melanoma based on the presence of endogenous stable free radicals in melanin pigments. Taking into account the abundance of these naturally occurring free radicals in proliferating melanocytes and their localization pattern, we hypothesized that electron paramagnetic resonance (EPR) imaging could be a unique tool for mapping melanomas with high sensitivity and high resolution. The potential of EPR to image melanoma samples was demonstrated in vitro in animal and human samples. Using EPR systems operating at low frequency, we were also able to record in vivo EPR spectra and images from the melanin present in a subcutaneous melanoma implanted in a mouse. In addition to the proof-of-concept and the achievement of providing the first non-invasive image of an endogenous radical, this technology may represent a key advance in improving the diagnosis of suspected melanoma lesions.

An Endogenous Electron Spin Resonance (ESR) Signal Discriminates Nevi from Melanomas in Human Specimens: A Step Forward in Its Diagnostic Application

“…ESR technique has been previously suggested for diagnosis and employed in melanoma research [41], [42], however the present study is the first reporting a clear association of a specific ESR signal to a large number (n = 52) of human melanomas using a large number of healthy controls (n = 60 nevi). Furthermore, a different eu/pheomelanin ratio in nevi vs melanomas “High Breslow” has been shown here for the first time, strongly supporting that qualitative melanin changes may occur in nevi as compared to melanomas with worst prognosis.…”

“…Early diagnosis is a key request in aggressive tumours such as melanoma; currently, trained dermatologists perform visual- and epiluminescence-based macroscopical inspection, and suspect melanoma is then confirmed by histological examination. ESR-based in situ analysis of pigmented skin lesions has been suggested as a possible non-invasive diagnostic tool, according to results obtained on melanoma cell lines and melanoma tissues [29], [39]–[41] and in animal models of melanoma [39], [42]. As possible melanoma markers, stable melanin granule-connected [29] or cellular membrane-associated [43] or UV-induced short living melanin- and oxygen-derived ESR signals have been proposed [44], [45].…”

The Contribution of Electron Paramagnetic Resonance to Melanoma Research

“…In 2008, Vanea et al [15] assessed the potential of EPR to image freeze-dried mouse cutaneous melanomas and lung metastases. The freeze-drying process was required to avoid a nonresonant absorption of the microwaves by the water in the 9 GHz EPR system.…”

Characterization of Melanin Radicals in Paraffin-embedded Malignant Melanoma and Nevus Pigmentosus Using X-band EPR and EPR Imaging

“…Thus, non-invasive EPRI can provide detailed information regarding the location and concentration of paramagnetic species in naturally occurring biomedical samples, such as melanin radicals in MM. Melanin radicals in MM have been studied using EPR methods in various ways, such as using low temperature and synthetic melanin, 7 animal models, [8][9][10][11] paraffin-embedded human melanoma, 12 and human specimens. 13 Melanin radicals in MM and NP were also compared using CW EPR.…”