Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Department of Radiology & Nuclear Medicine, VU University Medical Center, 1081 HV Amsterdam, The Netherlands.
Molecules. 2018 Mar 8;23(3):607. doi: 10.3390/molecules23030607.
Neuroinflammation, which involves microglial activation, is thought to play a key role in the development and progression of neurodegenerative diseases and other brain pathologies. Positron emission tomography is an ideal imaging technique for studying biochemical processes in vivo, and particularly for studying the living brain. Neuroinflammation has been traditionally studied using radiotracers targeting the translocator protein 18 kDa, but this comes with certain limitations. The current review describes alternative biological targets that have gained interest for the imaging of microglial activation over recent years, such as the cannabinoid receptor type 2, cyclooxygenase-2, the P2X₇ receptor and reactive oxygen species, and some promising radiotracers for these targets. Although many advances have been made in the field of neuroinflammation imaging, current radiotracers all target the pro-inflammatory (M1) phenotype of activated microglia, since the number of known biological targets specific for the anti-inflammatory (M2) phenotype that are also suited as a target for radiotracer development is still limited. Next to proceeding the currently available tracers for M1 microglia into the clinic, the development of a suitable radiotracer for M2 microglia would mean a great advance in the field, as this would allow for imaging of the dynamics of microglial activation in different diseases.
神经炎症涉及小胶质细胞的激活，被认为在神经退行性疾病和其他脑部病变的发展和进展中发挥关键作用。正电子发射断层扫描是研究体内生化过程的理想成像技术，特别是研究活体大脑的理想成像技术。神经炎症传统上使用针对 18 kDa 转位蛋白的放射性示踪剂进行研究，但这存在一定的局限性。本综述描述了近年来用于研究小胶质细胞激活的替代生物学靶点，例如大麻素受体 2、环氧化酶-2、P2X7 受体和活性氧，以及一些针对这些靶点的有前途的放射性示踪剂。尽管在神经炎症成像领域已经取得了许多进展，但目前的放射性示踪剂都靶向激活的小胶质细胞的促炎（M1）表型，因为针对抗炎（M2）表型的已知生物学靶点数量仍然有限，并且不适合作为放射性示踪剂开发的靶点。除了将目前用于 M1 小胶质细胞的放射性示踪剂推进临床应用外，开发用于 M2 小胶质细胞的合适放射性示踪剂将是该领域的重大进展，因为这将允许在不同疾病中对小胶质细胞激活的动态进行成像。
