RT Journal Article
SR Electronic
T1 Imaging of the 18 kDa translocator protein in an inflammation-prone mouse model using [11C]PBR28
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1815
OP 1815
VO 55
IS supplement 1
A1 Lao, Patrick
A1 Hillmer, Ansel
A1 Barnhart, Todd
A1 Puglielli, Luigi
A1 Farhoud, Mohammed
A1 Christian, Bradley
YR 2014
UL http://jnm.snmjournals.org/content/55/supplement_1/1815.abstract
AB 1815 Objectives Translocator protein (TSPO) is highly expressed on the outer membrane of the mitochondria in phagocytic inflammatory cells like reactive astrocytes and activated microglia. TSPO can be imaged by PET using [11C]PBR28. This work seeks to characterize the [11C]PBR28 kinetics in a mouse model that exhibits neurodegeneration. The standard uptake values (SUVs) were compared between mutant (AT-1S113R) and wild-type (AT-1WT) groups as an estimation of [11C]PBR28 binding in cases of neuroinflammation. Methods Four AT-1S113R mice and four AT-1WT underwent dynamic [11C]PBR28 PET scans with x-ray transmission scans in a Genesys4 PET scanner. Time-activity curves (TACs) were extracted from regions of interest (ROIs) placed over anterior, medial, and posterior brain regions, as well as the whole brain. Due to the lack of a reference region, SUVs were generated from data collected 40 to 60 minutes post-injection. SUVs were compared between groups. Results The SUVs for each ROI were significantly different (α=0.05) between groups. The AT-1WT mice exhibit faster brain clearance and reduced retention time of [11C]PBR28 than the AT-1S113R mice in all ROIs. The kinetics were independent of region (anterior, medial, posterior) within groups. The presence of reactive astrocytes and activated microglia were confirmed by immunolabeling with GRP and Iba1, respectively. Conclusions PET imaging of TSPO using [11C]PBR28 provides a convenient method for in vivo discrimination between the healthy and inflamed state of the brain. SUVs are a sensitive metric for the quantification of radiotracer uptake when reference regions are not available. Similar regional kinetics within groups indicates that the whole brain is a suitable ROI for widespread inflammation. Research Support RO1 AG028569, P50 AG033514, UW Alzheimer’s Disease Research Center, SciMed GRS Fellowship