Positron emission tomography imaging of dopamine D₂/₃ receptors in the human cortex with [¹¹C]FLB 457: reproducibility studies.
In a recent PET study, we demonstrated the ability to measure amphetamine-induced DA release in the human cortex with the relatively high affinity dopamine D₂/₃ radioligand [¹¹C]FLB 457 (Narendran et al., [2009] Synapse 63:447-461). The aim of this study was to evaluate the reproducibility and reliability of [¹¹C]FLB 457 in the same imaging paradigm we used to measure amphetamine-induced DA transmission. Six healthy human subjects (three males/three females)were studied twice with [¹¹C]FLB 457, once at baseline and again 3 h following the end of the baseline scan. D₂/₃ receptor binding parameters were estimated using a two-tissue compartment kinetic analysis in the cortical regions of interest and cerebellum (reference region). The test-retest variability and intraclass correlation coefficient were assessed for distribution volume (VT), binding potential relative to plasma concentration (BP(P)), and binding potential relative to non-displaceable uptake (BP(ND)) of [¹¹C]FLB 457. The test-retest variability of [¹¹C]FLB 457 VT, BPP, and BP(ND) were ≤15%, consistent with the published test-retest variability for this ligand in other brain regions (Sudo et al., [2001] Nucl Med Commun 22:1215-1221; Vilkman et al., [2000] Eur J Nucl Med 27:1666-1673). In addition, no significant decrease in [¹¹C]FLB457 BP(ND) was observed in the second scan compared to the first one. This suggests that the contribution of carryover mass of [¹¹C]FLB 457 to the measured reduction in[¹¹C]FLB 457 BP(ND) following amphetamine was relatively low. These data support the further validation of [¹¹C]FLB 457 as a tool to measure amphetamine-induced dopamine release in the human cortex.
Narendran
Rajesh
R
Department of Radiology, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA. narendranr@upmc.edu
Mason
N Scott
NS
May
Maureen A
MA
Chen
Chi-Min
CM
Kendro
Steve
S
Ridler
Khanum
K
Rabiner
Eugenii A
EA
Laruelle
Marc
M
Mathis
Chester A
CA
Frankle
W Gordon
WG
D000704:Analysis of Variance; D002250:Carbon Radioisotopes / Q000378:metabolism; D002540:Cerebral Cortex / Q000000981:diagnostic imaging* / Q000378:metabolism; D018492:Dopamine Antagonists / Q000378:metabolism; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D049268:Positron-Emission Tomography; D011759:Pyrrolidines / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D050637:Receptors, Dopamine D3 / Q000378:metabolism*; D015203:Reproducibility of Results; D012457:Salicylamides / Q000378:metabolism
D002250:Carbon Radioisotopes; D018492:Dopamine Antagonists; D011759:Pyrrolidines; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D012457:Salicylamides; C065065:FLB 457