van der Weijden Chris W J, Ahmed Ahmed K M A, van der Hoorn Anouk, Zhu Junqing, Wu Chunying, Wang Yanming, Stormezand Gilles N, Dierckx Rudi A J O, Meilof Jan F, de Vries Erik F J
Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Department of Radiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
J Nucl Med. 2025 Jan 3;66(1):136-141. doi: 10.2967/jnumed.123.266896.
Multiple sclerosis (MS) is a neurodegenerative disease characterized by demyelinated lesions in the brain and spinal cord. A few clinical studies using PET to image myelin in the brain have been performed, but none investigated the spinal cord. Because clinically relevant motor symptoms are primarily due to spinal cord damage, this translational study evaluated [C]-methyl-4,4'-diaminostilbene (MeDAS) as a PET tracer for myelin imaging in the rat and human spinal cord. [C]MeDAS PET of the spinal cord was conducted in experimental autoimmune encephalomyelitis, lysophosphatidylcholine, and spinal cord injury animal models of focal demyelination. Then, 6 healthy controls and 11 MS patients were subjected to MRI and [C]MeDAS PET of the spinal cord between C5 and T6 vertebrae. Regions of interest covering 100%, 60%, and 40% of the diameter of the spinal canal were drawn, and tracer uptake was normalized to the activity in the blood pool, muscle, or injected dose per unit of body weight (SUV). [C]MeDAS uptake was significantly reduced in spinal cord lesions in all animal models. In humans, tracer uptake was significantly higher in the cervical than the thoracic spinal cord, which corresponds well with the known physiologic rostral-caudal gradient in myelin density. MS patients had significantly lower [C]MeDAS uptake in the upper spinal cord (C5-T3) than did controls. The [C]MeDAS PET signal was inversely correlated with the presence of MS lesions in specific sections of the spinal cord. The best differentiation among regions with different myelin density was obtained when the smallest region of interest was used and spinal cord uptake was expressed as SUV. [C]MeDAS PET shows the potential to quantify myelin density in the spinal cord. It enables detection of physiologic differences in myelin density between spinal cord segments and between MS patients and healthy controls, which warrants further evaluation of this technique.
多发性硬化症（MS）是一种神经退行性疾病，其特征是大脑和脊髓中出现脱髓鞘病变。已经进行了一些使用正电子发射断层扫描（PET）对大脑中的髓鞘进行成像的临床研究，但没有一项研究脊髓。由于临床上相关的运动症状主要是由于脊髓损伤引起的，因此这项转化研究评估了[C] - 甲基 - 4,4'-二氨基芪（MeDAS）作为一种用于大鼠和人类脊髓髓鞘成像的PET示踪剂。在实验性自身免疫性脑脊髓炎、溶血磷脂酰胆碱和局灶性脱髓鞘的脊髓损伤动物模型中进行了脊髓的[C]MeDAS PET检查。然后，对6名健康对照者和11名MS患者进行了C5至T6椎体之间脊髓的MRI和[C]MeDAS PET检查。绘制了覆盖椎管直径100%、60%和40%的感兴趣区域，并将示踪剂摄取量归一化为血池、肌肉中的活性或每单位体重的注射剂量（标准化摄取值，SUV）。在所有动物模型中，脊髓病变部位的[C]MeDAS摄取均显著降低。在人类中，示踪剂在颈段脊髓的摄取显著高于胸段脊髓，这与已知的髓鞘密度从颅端到尾端的生理梯度非常吻合。MS患者上脊髓（C5 - T3）的[C]MeDAS摄取显著低于对照组。[C]MeDAS PET信号与脊髓特定节段MS病变的存在呈负相关。当使用最小的感兴趣区域并将脊髓摄取量表示为SUV时，在不同髓鞘密度区域之间获得了最佳区分。[C]MeDAS PET显示出量化脊髓髓鞘密度的潜力。它能够检测脊髓节段之间以及MS患者与健康对照者之间髓鞘密度的生理差异，这值得对该技术进行进一步评估。
