Melanoma incidence continues increasing, with 7910 deaths from 55,100 new cases in 2004 alone in the US. Early, rapid, accurate and cost-effective diagnosis, imaging and staging is central to the effective application of developing melanoma therapies, yet current imaging techniques lack either tissue penetration or lack melanoma specificity, when clearly both are needed. In addition to melanin's pigmentary properties, that allow specific but only superficial optical imaging of melanoma, melanin contains high concentrations of stable free radicals formed during its synthesis. These melanin radicals can be sensitively and specifically detected and identified by Electron Paramagnetic Resonance spectroscopy (EPR). We hypothesize that newly-developed, low frequency In vivo EPR techniques of high sensitivity can detect and image even thick (10mm) melanoma using the inherent molecular contrast of melanin, to allow rapid, noninvasive melanoma detection, imaging and staging. Our preliminary data has shown that this is feasible and we propose these studies to develop this approach:
Specific Aim 1. Optimize in vivo EPR spectroscopic techniques to detect primary cutaneous melanotic lesions. We will induce cutaneous melanomas in the mammal Monodelphis domestica by dimethylbenzanthracene application, and use 1GHz EPR spectroscopy with both surface and whole body coils to detect the melanin EPR signal in melanotic lesions.
Specific Aim 2. Apply EPR imaging to image melanomas. Using the above melanoma model, we will apply magnetic field gradients to allow spatial imaging of melanoma thickness, depth and margins We will then correlate EPR images with histological measurements, and the quality of dimensional and morphological correlation studied as a function of instrumental and experimental factors. This proposal will enable development of this innovative technique to rapidly and accurately detect and image melanoma, nonivasively, yet with molecular specificity, paving the way for clinical trials of efficacy. ? ?
| Lund, Leslie; Ley, Ronald D; Felton, Linda A et al. (2007) Determination of wavelength-specific UV protection factors of sunscreens in intact skin by EPR measurement of UV-induced reactive melanin radical. Photochem Photobiol 83:952-7 |
| Lund, Leslie P; Timmins, Graham S (2007) Melanoma, long wavelength ultraviolet and sunscreens: controversies and potential resolutions. Pharmacol Ther 114:198-207 |
| Durant, Stephen T; Paffett, Kimberly S; Shrivastav, Meena et al. (2006) UV radiation induces delayed hyperrecombination associated with hypermutation in human cells. Mol Cell Biol 26:6047-55 |
