RT Journal Article
SR Electronic
T1 [11C]SSR180575: Preliminary evaluation in rodent models of neuroinflammation
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1218
OP 1218
VO 50
IS supplement 2
A1 Fabien Chauveau
A1 Herve Boutin
A1 Nadja Van Camp
A1 Cyrille Thominiaux
A1 Philippe Hantraye
A1 Thomas Rooney
A1 Jesus Benavides
A1 Frederic Dolle
A1 Bertrand Tavitian
YR 2009
UL http://jnm.snmjournals.org/content/50/supplement_2/1218.abstract
AB 1218 Objectives To evaluate the PBR ligand [11C]SSR180575 in an acute and chronic model for neuroinflammation as compared to the reference [11C]PK11195. Methods SSR180575 was labeled with carbon-11. For acute and chronic neuroinflammation we used respectively the AMPA rat model (n=14) (Boutin JNM 2007) and double transgenic mice (APP×PS1, n=15) for Alzheimer’s disease at the age of 12 months. All animals were scanned using the Concorde Focus 220 µPET scanner. Both rat and mouse models were divided in 4 equal groups to study the brain kinetics of [11C]PK11195 and [11C]SSR180575, and the specificity of the binding by displacement studies using an excess (1 mg/kg) of non-labeled PK11195 or SSR180575. Additional to in vivo studies we performed in vitro autoradiography on the same models. Results In rats, the uptake ratio of [11C]SSR180575 in the lesioned-over intact striatum was significantly higher for [11C]SSR180575 than [11C]PK11195. Competition with PK11195 or SSR180575 quickly displaced the tracer from the lesioned side. Autoradiography on brain sections confirmed the in vivo results with a high ipsi- to contralateral ratio (3.8), which was abolished by an excess of PK11195 or SSR180575. In both PS1 and APPxPS1 mice, [11C]SSR180575 uptake in the whole brain was higher as compared to the uptake of [11C]PK11195. In addition, in vitro autoradiography showed high specific binding in APPxPS1 mice that was double the binding of PS1 mice. Conclusions The results obtained confirm the potential of [11C]SSR180575 to image neuroinflammation.