MOLECULAR IMAGING OF MELANOMA BY EPR

描述（由申请人提供）：黑色素瘤发病率持续增加，仅在美国，2004年就有55，100例新发病例中有7910例死亡。早期，快速，准确和具有成本效益的诊断，成像和分期是开发黑色素瘤疗法的有效应用的核心，但目前的成像技术缺乏组织穿透或缺乏黑色素瘤特异性，当两者都需要时。除了黑色素的色素性质，允许黑色素的特异性但仅表面的光学成像，黑色素含有在其合成期间形成的高浓度的稳定自由基。这些黑色素自由基可以通过电子顺磁共振光谱（EPR）灵敏和特异地检测和鉴定。我们假设，新开发的低频率高灵敏度的体内EPR技术可以使用黑色素的固有分子对比度检测和成像甚至厚（10 mm）的黑色素瘤，以允许快速，非侵入性的黑色素瘤检测，成像和分期。我们的初步数据表明，这是可行的，我们建议这些研究来开发这种方法：具体目标1。优化体内EPR光谱技术，以检测原发性皮肤黑色素病变。我们将通过应用二甲基苯并蒽在哺乳动物Monodelphis astritica中诱导皮肤黑色素瘤，并使用具有表面和全身线圈的1GHz EPR光谱来检测黑色素病变中的黑色素EPR信号。具体目标2。应用EPR成像对黑色素瘤进行成像。使用上述黑色素瘤模型，我们将应用磁场梯度，以允许黑色素瘤厚度，深度和边缘的空间成像。然后将EPR图像与组织学测量相关联，并将尺寸和形态相关性的质量作为仪器和实验因素的函数进行研究。该提案将使这种创新技术的发展，以快速，准确地检测和成像黑色素瘤，非侵入性，但具有分子特异性，为临床试验的疗效铺平了道路。

DESCRIPTION (provided by applicant): 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.