J Nucl Med. 2007; 48 (Supplement 2):113P
Neurosciences: Basic Science
Dopamine and Nicotinic Receptor Imaging |
Correlation between PET and microdialysis measurements of amphetamine induced DA release in striatal and extrastriatal brain regions in baboons
Mark Slifstein1,
Holly Moore1,
Lawrence Kegeles1,
Michelle Duvall2,
Xiaoyan Xu2,
Elizabeth Hackett2,
John Castrillon2,
Olga Kambalov2,
Erica Scher2,
Marc Laruelle1 and
Anissa Abi-Dargham1
1 Psychiatry, Columbia University, New York, New York; ;
2 New York State Psychiatric Institute, New York, New York
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Objectives: The amphetamine challenge (AMPH) is a frequently used paradigm for estimating dopamine (DA) release non-invasively in the brain by measuring changes in specific binding of radioligands for D2/D3 receptors. Previous studies have correlated the change in radioligand binding with DA efflux increases following AMPH as measured by microdialysis using radioligands that can only image the striatum. Fallypride (C11 or F18) provides quantifiable images in striatum and extrastrial regions. Here we measured the correlation between changes in [11C] fallypride binding and DA efflux increases following AMPH in baboons. Methods: Three female baboons (A, B and C) were anesthetized and scanned for 2 hr on the HR+ following a bolus injection of [11C] fallypride. After 1 additional hour, amphetamine was administered as a bolus (1 mg/kg ,A and B and 1.5 mg/kg, C). The post AMPH scan began 
hr following AMPH administration. The parameter V3" was obtained by SRTM with cerebellum as reference region. Change following AMPH was quantified as V3"_post/V3"_ pre – 1 (
V3"). Microdialysis was later performed on 2 of the animals (A and C) using the same anesthesia protocol. Probes were placed in striatum, anterior cingulate and thalamus and perfused with aCSF. After probe equilibration, dialysates were collected every 15 min. After 1 hr, animals received the same AMPH dose as during the PET study, and 3 more dialysates were collected. DA concentration was quantified by HPLC-ED. Post-AMPH values were expressed as % increase relative to mean pre-AMPH samples (DA). Average regional DA was correlated with V3" within and across subjects. Results: Regional V3" was highly correlated with DA, both within and across animals: DA = -46.4*V3" – 7.7 for animal A (R2 = 0.97), -12.6*V3" +2.0 for animal C (R2 = 0.80) and -21.7*V3" -0.4 across all 3 animals (R2 = 0.91). Mean V3" was -19 ± 10%, -9 ± 7% and -3 ± 17% in striatum, thalamus and cingulate. Conclusions: The high correlation between V3" and DA supports the validity of PET measurements of DA release following AMPH in extrastriatal regions as well as striatum using fallypride.
Research Support (if any): MH0661710-03
