In vivo PET imaging of the neuroinflammatory response in rat spinal cord injury using the TSPO tracer [18F]GE-180 and effect of docosahexaenoic acid

• Published in: European journal of nuclear medicine and molecular imaging 2016-08, Vol.43 (9), p.1710-1722
• Main Authors: Tremoleda, J. L., Thau-Zuchman, O., Davies, M., Foster, J., Khan, I., Vadivelu, K. C., Yip, P. K., Sosabowski, J., Trigg, W., Michael-Titus, A. T.
• Format: Article
• Language: English
• Subjects: Acids; Animals; Carbazoles - metabolism; Carbazoles - pharmacokinetics; Cardiology; Carrier Proteins - metabolism; Docosahexaenoic Acids - pharmacology; Fluorine Radioisotopes; Imaging; Inflammatory diseases; Male; Medical imaging; Medicine; Medicine & Public Health; Neurology; Neuroprotective Agents - pharmacology; Nuclear Medicine; Oncology; Original; Original Article; Orthopedics; Positron-Emission Tomography; Radiology; Rats; Rats, Wistar; Receptors, GABA-A - metabolism; Rodents; Spinal cord injuries; Spinal Cord Injuries - diagnostic imaging; Spinal Cord Injuries - metabolism; Spinal Cord Injuries - physiopathology; Tissue Distribution
• ISSN: 1619-7070; 1619-7089
• DOI: 10.1007/s00259-016-3391-8

Purpose Traumatic spinal cord injury (SCI) is a devastating condition which affects millions of people worldwide causing major disability and substantial socioeconomic burden. There are currently no effective treatments. Modulating the neuroinflammatory (NI) response after SCI has evolved as a major therapeutic strategy. PET can be used to detect the upregulation of the 18-kDa translocator protein (TSPO), a hallmark of activated microglia in the CNS. We investigated whether PET imaging using the novel TSPO tracer [ 18 F]GE-180 can be used as a clinically relevant biomarker for NI in a contusion SCI rat model, and we present data on the modulation of NI by the lipid docosahexaenoic acid (DHA). Methods A total of 22 adult male Wistar rats were subjected to controlled spinal cord contusion at the T10 spinal cord level. Six non-injured and ten T10 laminectomy only (LAM) animals were used as controls. A subset of six SCI animals were treated with a single intravenous dose of 250 nmol/kg DHA (SCI-DHA group) 30 min after injury; a saline-injected group of six animals was used as an injection control. PET and CT imaging was carried out 7 days after injury using the [ 18 F]GE-180 radiotracer. After imaging, the animals were killed and the spinal cord dissected out for biodistribution and autoradiography studies. In vivo data were correlated with ex vivo immunohistochemistry for TSPO. Results In vivo dynamic PET imaging revealed an increase in tracer uptake in the spinal cord of the SCI animals compared with the non-injured and LAM animals from 35 min after injection ( P