Division of Hematology/Oncology, Department of Medicine, and Department of Radiology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
Mol Imaging. 2010 Jun;9(3):128-40.
Low back pain is a prevalent medical condition that is difficult to diagnose and treat. Current imaging methods are unable to correlate pain reliably with spinal structures, and surgical removal of painful damaged or degenerating disks is technically challenging. A contrast agent specific for the intervertebral disk could assist in the detection, diagnosis, and surgical treatment of low back pain. The styryl pyridinium (FM) fluorophores were characterized and structure-activity relationships between chemical structure and in vivo uptake were established. Two novel FM fluorophores with improved optical properties for imaging the intervertebral disks were synthesized and evaluated in mice, rats, and pigs. After a single systemic injection, eight of eight FM fluorophores provided high-contrast imaging of the trigeminal ganglia, whereas six of eight provided high-contrast imaging of the dorsal root ganglia. Unexpectedly, three of eight FM fluorophores provided high-contrast imaging of annulus fibrosus tissue of the intervertebral disks, confirmed histologically. We present the first known contrast agent specific for the intervertebral disks and identify the chemical structural motif that mediates uptake. FM fluorophores could be used for image-guided surgery to assist in the removal of intervertebral disk and lay the foundation for derivatives for magnetic resonance imaging and positron emission tomography.
下背痛是一种常见的医学病症,难以诊断和治疗。目前的成像方法无法可靠地将疼痛与脊柱结构相关联,而且手术切除疼痛受损或退化的椎间盘具有技术挑战性。一种专门针对椎间盘的造影剂可以协助检测、诊断和治疗下背痛。本文对 styryl pyridinium (FM) 荧光团进行了表征,并建立了化学结构与体内摄取之间的构效关系。合成了两种具有改进的椎间盘成像光学性能的新型 FM 荧光团,并在小鼠、大鼠和猪中进行了评估。单次系统注射后,8 种 FM 荧光团中有 8 种可提供三叉神经节的高对比度成像,而 8 种中有 6 种可提供背根神经节的高对比度成像。出乎意料的是,8 种 FM 荧光团中有 3 种可提供椎间盘纤维环组织的高对比度成像,这在组织学上得到了证实。本文首次报道了专门针对椎间盘的造影剂,并确定了介导摄取的化学结构基序。FM 荧光团可用于图像引导手术,以协助切除椎间盘,并为磁共振成像和正电子发射断层扫描的衍生物奠定基础。