Dopamine transporter binding in rat striatum: a comparison of [O-methyl-11C]beta-CFT and [N-methyl-11C]beta-CFT.
BACKGROUND
Positron emission tomography scanning with radiolabeled phenyltropane cocaine analogs is important for quantifying the in vivo density of monoamine transporters, including the dopamine transporter (DAT). [(11)C]beta-CFT is useful for studying DAT as a marker of dopaminergic innervation in animal models of psychiatric and neurological disorders. [(11)C]beta-CFT is commonly labeled at the N-methyl position. However, labeling of [(11)C]beta-CFT at the O-methyl position is a simpler procedure and results in a shorter synthesis time [desirable in small-animal studies, where specific activity (SA) is crucial]. In this study, we sought to validate that the O-methylated form of [(11)C]beta-CFT provides equivalent quantitative results to that of the more commonly reported N-methyl form.


METHODS
Four female Sprague-Dawley rats were scanned twice on the IndyPET II small-animal scanner, once with [N-methyl-(11)C]beta-CFT and once with [O-methyl-(11)C]beta-CFT. DAT binding potentials (BP identical withB'(avail)/K(d)) were estimated for right and left striata with a nonlinear least-squares algorithm, using a reference region (cerebellum) as the input function.


RESULTS
[N-Methyl-(11)C]beta-CFT and [O-methyl-(11)C]beta-CFT were synthesized with 40-50% radiochemical yields (HPLC purification). Radiochemical purity was >99%. SA at end of bombardment was 258+/-30 GBq/micromol. Average BP values for right and left striata with [N-methyl-(11)C]beta-CFT were 1.16+/-0.08 and 1.23+/-0.14, respectively. BP values for [O-methyl-(11)C]beta-CFT were 1.18+/-0.08 (right) and 1.22+/-0.16 (left). Paired t tests demonstrated that labeling position did not affect striatal DAT BP.


CONCLUSIONS
These results suggest that [O-methyl-(11)C]beta-CFT is quantitatively equivalent to [N-methyl-(11)C]beta-CFT in the rat striatum.
Yoder
Karmen K
KK
Department of Radiology, Indiana University School of Medicine, L3-208, Indianapolis, IN 46202, USA.
Hutchins
Gary D
GD
Mock
Bruce H
BH
Fei
Xiangshu
X
Winkle
Wendy L
WL
Gitter
Bruce D
BD
Territo
Paul R
PR
Zheng
Qi-Huang
QH
D000818:Animals; D002250:Carbon Radioisotopes / Q000737:chemistry; D003042:Cocaine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism*; D005260:Female; D017072:Neostriatum / Q000000981:diagnostic imaging / Q000378:metabolism*; D009584:Nitrogen / Q000737:chemistry*; D010100:Oxygen / Q000737:chemistry*; D049268:Positron-Emission Tomography; D011485:Protein Binding; D011854:Radiochemistry; D051381:Rats; D017207:Rats, Sprague-Dawley
D002250:Carbon Radioisotopes; D050483:Dopamine Plasma Membrane Transport Proteins; C021279:(1R-(exo,exo))-3-(4-fluorophenyl)-8-methyl-8- azabicyclo(3.2.1)octane-2-carboxylic acid, methyl ester; D003042:Cocaine; D009584:Nitrogen; D010100:Oxygen