MOLECULAR IMAGING OF MELANOMA BY EPR

描述(申请人提供)：黑色素瘤发病率继续上升，仅在2004年美国就有55,100例新病例中有7910例死亡。早期、快速、准确和经济有效的诊断、成像和分期是开发黑色素瘤治疗方法的有效应用的核心，然而目前的成像技术要么缺乏组织穿透性，要么缺乏黑色素瘤特异性，而这两者显然都是必要的。除了黑色素的色素特性外，黑色素还含有在合成过程中形成的高浓度稳定的自由基，这使得黑色素瘤可以进行特殊但仅是表面的光学成像。这些黑色素自由基可以通过电子顺磁共振波谱(EPR)灵敏而特异地检测和识别。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固有的分子对比度来检测和成像甚至厚(10 Mm)的黑色素瘤，从而实现快速、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，我们建议通过这些研究来发展这一方法：特定目的1.优化体内EPR光谱技术以检测原发皮肤黑色素性皮损。我们将通过应用二甲基苯并菲诱导哺乳动物Monodelphis家用皮肤黑色素瘤，并使用1 GHz表面和全身线圈的EPR光谱来检测黑色素病变中的黑色素EPR信号。具体目的2.将EPR成像应用于影像黑色素瘤。使用上面的黑色素瘤模型，我们将应用磁场梯度来实现黑色素瘤厚度、深度和边缘的空间成像。然后，我们将把EPR图像与组织学测量相关联，并研究作为仪器和实验因素的函数的尺寸和形态相关性的质量。这项提议将使这项创新技术的发展能够快速、准确地检测和成像黑色素瘤，非侵入性，但具有分子特异性，为疗效的临床试验铺平道路。

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.