RT Journal Article
SR Electronic
T1 Correlation between PET and microdialysis measurements of amphetamine induced DA release in striatal and extrastriatal brain regions in baboons
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 113P
OP 113P
VO 48
IS supplement 2
A1 Mark Slifstein
A1 Holly Moore
A1 Lawrence Kegeles
A1 Michelle Duvall
A1 Xiaoyan Xu
A1 Elizabeth Hackett
A1 John Castrillon
A1 Olga Kambalov
A1 Erica Scher
A1 Marc Laruelle
A1 Anissa Abi-Dargham
YR 2007
UL http://jnm.snmjournals.org/content/48/supplement_2/113P.2.abstract
AB 382 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 ½ 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 (ΔV3”). 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 (ΔDA). Average regional ΔDA was correlated with ΔV3" within and across subjects. Results: Regional ΔV3” was highly correlated with ΔDA, both within and across animals: ΔDA = -46.4*ΔV3” – 7.7 for animal A (R2 = 0.97), -12.6*ΔV3” +2.0 for animal C (R2 = 0.80) and -21.7*ΔV3” -0.4 across all 3 animals (R2 = 0.91). Mean ΔV3” was -19 ± 10%, -9 ± 7% and -3 ± 17% in striatum, thalamus and cingulate. Conclusions: The high correlation between ΔV3” and ΔDA 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