RT Journal Article
SR Electronic
T1 Detection of cytotoxic activation of microglia in a rat neuroinflammation model using a novel translocator protein ligand, [18F]FEPPA
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1884
OP 1884
VO 53
IS supplement 1
A1 Masahiko Nomura
A1 Hiroshi Toyama
A1 Hiromi Suzuki
A1 Takashi Yamada
A1 Seiichiro Ota
A1 Masanori Ichise
A1 Alan Wilson
A1 Makoto Sawada
A1 Kengo Ito
A1 Kentaro Hatano
YR 2012
UL http://jnm.snmjournals.org/content/53/supplement_1/1884.abstract
AB 1884 Objectives Activated microglia are known to increase the expression of translocator protein (18 kDa) (TSPO). We evaluated whether a novel TSPO ligand, [18F]FEPPA could detect microglia in the cytotoxic state for acute reaction in rat neuroinflammation model. Methods Nineteen rats (10 LPS, 9 vehicle) had 6-OHDA injected into the right striatum (ST). On day 4, 1st PET scans were performed for 60 min with an animal PET/CT scanner after an injection of [18F]FEPPA. Then lipopolysaccharide(LPS) for acute reaction or vehicle were administered intraperitoneally. After 4 hrs, PET scans were repeated. Rats were then euthanized and immunohistochemical staining and RT-PCR for inflammatory cytokines (TNFα, IL-1β) were performed for confirmation of the microglial activation and cytotoxic damage. Regions of interest were placed over the ST bilaterally on [18F]FEPPA PET images. Right/left (R/L) ST uptake ratios (30-60min) were compared between LPS and vehicle groups (gps). Results In 1st PET scans, the R/L ST ratios in LPS gp (1.17 ± 0.15) were not significantly different from vehicle gp (1.12 ± 0.10)(p=0.37). However, in Repeated PET scans, the R/L ST ratios in LPS gp (1.31 ± 0.26) were significantly higher than in vehicle gp (1.09 ± 0.14)(p=0.04). Percent increase of the R/L ST ratios in each gp between 1st and repeated PET scans were significantly higher in LPS gp (11.6 ± 12.0) than in vehicle gp (-1.5 ± 14.1)(p=0.04). Activated microglia was exclusively observed on R ST in both LPS and vehicle gps histochemically. LPS gp showed higher expression of inflammatory cytokines than in vehicle gp indicating cytotoxic activation was induced by LPS treatment. Conclusions These results suggest that TSPO binding as measured by [18F]FEPPA PET appears a promising for detection of cytotoxic activation of microglia in a rat neuroinflammation model