Reduced dimethylaminoethanol in [(18)F]fluoromethylcholine: an important step towards enhanced tumour visualization.
OBJECTIVE
[(18)F]Fluoromethylcholine ([(18)F]FCho) is a radiotracer generally used for tumour visualization in patients. Due to high levels of dimethylaminoethanol (DMAE) remaining in [(18)F]FCho solutions synthesized by currently available methods, tumour visualization might be compromised.


METHODS
An improved purification method involving an optimized purification step for reducing the levels of DMAE was conceived. The physiological explanation for the interference of residual DMAE in [(18)F]FCho pharmacokinetics was further elaborated in a xenograft mouse model.


RESULTS
The use of a series of polymer solid-phase extraction cartridges (Oasis HLB/WCX), instead of the commonly used combination of tC18 and Accell CM cartridges, reduced DMAE levels from 402.2±49.6 ppm to 3.0±0.5 ppm. Subsequent in vitro tests proved that (1) [(18)F]FCho uptake was reduced in the presence of DMAE at concentrations above 0.5 µM and (2) DMAE is a competitive inhibitor of [(18)F]FCho transport. In vivo experiments in xenograft mouse models corroborated reduced tumour uptake at DMAE plasma levels of about 2.5 µM as found in patients injected with contaminated [(18)F]FCho.


CONCLUSIONS
Residual DMAE, even at levels below choline plasma concentrations found during fasting, compromises [(18)F]FCho uptake in vivo and care should be taken to avoid its interference in molecular imaging with [(18)F]FCho.
Slaets
Dominique
D
Ghent University, Harelbekestraat 72, 9000, Ghent, Belgium. Dominique.Slaets@ugent.be
De Bruyne
Sylvie
S
Dumolyn
Caroline
C
Moerman
Lieselotte
L
Mertens
Koen
K
De Vos
Filip
F
D000818:Animals; D016477:Artifacts; D001692:Biological Transport; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic; D005591:Chemical Fractionation / Q000379:methods*; D002794:Choline / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D003642:Deanol / Q000302:isolation & purification*; D005260:Female; D005910:Glioma / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D057054:Molecular Imaging / Q000379:methods*
C516370:fluoromethylcholine; D003642:Deanol; D002794:Choline