[11C]PK11195 PET imaging of spinal glial activation after nerve injury in rats

• Published in: NeuroImage (Orlando, Fla.) Vol. 79; pp. 121 - 128
• Main Authors: Imamoto, Natsumi, Momosaki, Sotaro, Fujita, Masahide, Omachi, Shigeki, Yamato, Hiroko, Kimura, Mika, Kanegawa, Naoki, Shinohara, Shunji, Abe, Kohji
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01.10.2013; Elsevier; Elsevier Limited
• Subjects: Animals; Behavior; Biological and medical sciences; Carrier Proteins - metabolism; Fundamental and applied biological sciences. Psychology; Isoquinolines - pharmacokinetics; Male; Microglia; Microglia - diagnostic imaging; Microglia - metabolism; Pain management; Partial sciatic nerve ligation (PSL); Peripheral Nerve Injuries - diagnostic imaging; Peripheral Nerve Injuries - metabolism; PK11195; Positron emission tomography (PET); Positron-Emission Tomography - methods; Radiopharmaceuticals - pharmacokinetics; Rats; Rats, Sprague-Dawley; Receptors, GABA-A - metabolism; Reproducibility of Results; Rodents; Sciatic Neuropathy - diagnostic imaging; Sciatic Neuropathy - metabolism; Sensitivity and Specificity; Spinal cord; Spinal Cord - diagnostic imaging; Spinal Cord - metabolism; Studies; Surgery; Translocator protein 18 kDa (TSPO); Vertebrates: nervous system and sense organs; Partial sciatic nerve ligation (PSL); Translocator protein 18kDa (TSPO); Spinal cord; Positron emission tomography (PET); PK11195; Microglia; Rat; Neuroglia; Rodentia; Central nervous system; Spinal nerve; Protein; Vertebrata; Mammalia; Animal; Imaging; Translocator protein 18 kDa (TSPO); Lesion; Sciatic nerve; Emission tomography
• ISSN: 1053-8119; 1095-9572
• DOI: 10.1016/j.neuroimage.2013.04.039

The role of glial activation has been implicated in the development and persistence of neuropathic pain after nerve injury by recent studies. PK11195 binding to the translocator protein 18kDa (TSPO) has been shown to be enhanced in activated microglia. This study was designed to assess PK11195 imaging in spinal microglia during activation after nerve injury. The development of neuropathic pain was induced by partial sciatic nerve ligation (PSL). PSL rats on days 7 and 14 after nerve injury were subjected to imaging with a small-animal positron emission tomography/computed tomography (PET/CT) scanner using [11C]PK11195 to detect spinal microglial activation by means of noninvasive in vivo imaging. Spinal [3H]PK11195 autoradiography was performed to confirm the results of [11C]PK11195 PET in PSL rats. Quantitative RT-PCR of CD11b and GFAP mRNA, and the immunohistochemistry of Iba1 and GFAP were investigated to detect activated microglia and astrocytes. Mechanical allodynia was observed in the ipsilateral paw of PSL rats from day 3 after nerve injury and stably persisted from days 7 to 14. PET/CT fusion images clearly showed large amounts of accumulation of [11C]PK11195 in the lumbar spinal cord on days 7 and 14 after nerve injury. [11C]PK11195 enhanced images were restricted to the L3–L6 area of the spinal cord. The standardized uptake value (SUV) of [11C]PK11195 was significantly increased in the lumbar spinal cord compared to that of the thoracic region. Increased specific binding of [11C]PK11195 to TSPO in the spinal cord of PSL rats was confirmed by competition studies using unlabeled (R, S)-PK11195. Increased [3H]PK11195 binding was also observed in the ipsilateral dorsal horn of the L3–L6 spinal cord on days 7 and 14 after nerve injury. CD11b mRNA and Iba1 immunoreactive cells increased significantly on days 7 and 14 after nerve injury by PSL. However, changes in GFAP mRNA and immunoreactivity were slight in the ipsilateral side of PSL rats. In the present study, we showed that glial activation could be quantitatively imaged in the spinal cord of neuropathic pain rats using [11C]PK11195 PET, suggesting that high resolution PET using TSPO-specific radioligands might be useful for imaging to assess the role of glial activation, including neuroinflammatory processes, in neuropathic pain patients. •Partial sciatic nerve ligation (PSL) produced mechanical allodynia.•Enhanced [11C]PK111195 uptake was observed in lumbar spinal cord of PSL rats.•Activation of spinal microglia and astrocyte was observed in PSL rats.•Spinal glial activation might be quantitatively detected by [11C]PK11195 PET.