TY - JOUR T1 - Metabolic-dopaminergic mapping of the quinolinic acid rat model of Huntington’s disease JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 249P LP - 249P VL - 48 IS - supplement 2 AU - Cindy Casteels AU - Emili Martinez AU - Maria Lluïsa Camon AU - Karolien Goffin AU - Nuria de Vera AU - Guy Bormans AU - Veerle Baekelandt AU - Anna Planas AU - Koen Van Laere Y1 - 2007/05/01 UR - http://jnm.snmjournals.org/content/48/supplement_2/249P.2.abstract N2 - 1152 Objectives: The quinolinic acid (QA) lesion rat model is a well-known acute model for Huntington’s disease (HD). We have characterized in vivo metabolic and dopamine D2 receptor changes in this model and investigated metabolic alterations in correlation to disease severity. Methods: 20 Wistar rats (female; 10 QA and 10 sham animals (PBS); age 16-18w) were investigated. QA (240nmol/μl) and PBS were stereotactically injected in the left caudate-putamen (CPu). MicroPET acquisitions were conducted on a FOCUS 220 system at 15-26 weeks post lesioning after 50 mg/kg pentobarbital IP anaesthesia, and using 18 MBq of 18F-FDG (n=20; 40min, 60min p.i.) and 11C-Raclopride (n=20; 60min dynamic). Parametric maps of 11C-Raclopride were generated and 18F-FDG was normalized to whole-brain uptake. Data were spatially normalized to Paxinos space and analyzed using SPM2. Results: Glucose metabolism and D2 receptor binding were reduced in the ipsilateral CPu by 35% and 77% respectively (all pheight≤2.10-11), while an increase for these markers was seen in the contralateral CPu (>6%, all pheight≤2.10-4). Relative metabolism was also increased in the contralateral hippocampus, thalamus and sensory-motor cortex (pheight=1.10-6). Correlation analysis revealed a positive relation between D2 impairment and metabolic activity in the ipsilateral CPu (p<1.10-4, small volume corrected). Conclusions: In vivo cerebral microPET mapping in QA rats points to a functional plasticity with recruitment of parallel motor circuits to compensate for the functional deficit of the ipsilateral striatocortical motor loop. The data is consistent with the destruction of interneurons and output neurons in the CPu that are known to have high levels of D2 receptors and may therefore be used for further in vivo evaluation of therapeutic modulatory approaches. Research Support (if any): Research Council of the K.U.Leuven (OT/05/58), the Flemish Fund for Scientific Research (FWO/G.0548.06). This work is performed under European Commission FP6-project DiMI,LSHB-CT-2005-512146. ER -