Department of Radiology, School of Medicine, Gifu University, 1-1 Yanagido, Gifu 501-1194, Japan; Innovation Center for Medical Redox Navigation, Kyushu University, Japan.
Japan Redox Inc., 4-29 Chiyo, Fukuoka 812-0044, Japan.
Free Radic Biol Med. 2019 Apr;134:99-105. doi: 10.1016/j.freeradbiomed.2019.01.002. Epub 2019 Jan 5.
Melanin is a pigment that includes free radicals and is widely distributed in living animals. Malignant melanoma is one of the most progressive tumors in humans with increasing incidence worldwide, and has shown resistance to chemotherapy, resulting in high mortality at the metastatic stage. In general, melanoma involves the abnormal accumulation of melanin pigment produced by malignant melanocytes. Electron paramagnetic resonance (EPR) spectroscopy and imaging is a powerful technique to directly visualize melanomas using endogenous free radicals in the melanin pigment. Because melanin radicals have a large linewidth, the low spatial resolution of EPR imaging results in blurred images and a lack of anatomical information. Dynamic nuclear polarization (DNP)-MRI is a noninvasive imaging method to obtain the spatio-temporal information of free radicals with MRI anatomical resolution. Proton signals in tissues, including free radicals, can be dramatically enhanced by EPR irradiation at the resonance frequency of the free radical prior to applying the MRI pulse sequence. However, the DNP effects of free radicals in the pigment of living organisms is unclear. Therefore, if endogenous free radicals in melanin pigment could be utilized as a bio-probe for DNP-MRI, this will be an advantage for the specific enhancement of melanoma tissues and might allow the separate noninvasive visualization of melanoma tissues without the need for probe administration. Here, we report that biological melanin pigment induced a in vivo DNP effect by interacting with water molecules. In addition, we demonstrated in vivo melanoma imaging based on the DNP effects of endogenous free radicals in the melanin pigment of living mice.
黑色素是一种包含自由基的色素，广泛分布于活体动物中。恶性黑色素瘤是人类中最具侵袭性的肿瘤之一，其发病率在全球范围内呈上升趋势，并且对化疗具有耐药性，导致转移阶段的死亡率很高。一般来说，黑色素瘤涉及恶性黑素细胞产生的黑色素色素的异常积累。电子顺磁共振（EPR）光谱和成像技术是一种使用黑色素色素中的内源性自由基直接可视化黑色素瘤的强大技术。由于黑色素自由基具有较大的线宽，EPR 成像的低空间分辨率导致图像模糊且缺乏解剖学信息。动态核极化（DNP）-MRI 是一种非侵入性成像方法，可利用 MRI 解剖分辨率获得自由基的时空信息。在施加 MRI 脉冲序列之前，用 EPR 在自由基的共振频率下照射组织中的质子信号（包括自由基），可以显著增强质子信号。然而，活体生物组织中自由基的 DNP 效应尚不清楚。因此，如果黑色素色素中的内源性自由基可以用作 DNP-MRI 的生物探针，这将是特异性增强黑色素瘤组织的优势，并且可能允许无需探针给药即可单独进行黑色素瘤组织的无创可视化。在这里，我们报告了生物黑色素色素通过与水分子相互作用诱导体内 DNP 效应。此外，我们还基于活鼠黑色素色素中内源性自由基的 DNP 效应展示了体内黑色素瘤成像。
