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Reduced dimethylaminoethanol in [18F]fluoromethylcholine: an important step towards enhanced tumour visualization

Dominique Slaets (UGent) , SYLVIE DE BRUYNE (UGent) , Caroline Dumolyn (UGent) , Lieselotte Moerman (UGent) , Koen Mertens (UGent) and Filip De Vos (UGent)
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Abstract
[F-18]Fluoromethylcholine ([F-18]FCho) is a radiotracer generally used for tumour visualization in patients. Due to high levels of dimethylaminoethanol (DMAE) remaining in [F-18]FCho solutions synthesized by currently available methods, tumour visualization might be compromised. 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 [F-18]FCho pharmacokinetics was further elaborated in a xenograft mouse model. 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) [F-18]FCho uptake was reduced in the presence of DMAE at concentrations above 0.5 A mu M and (2) DMAE is a competitive inhibitor of [F-18]FCho transport. In vivo experiments in xenograft mouse models corroborated reduced tumour uptake at DMAE plasma levels of about 2.5 A mu M as found in patients injected with contaminated [F-18]FCho. Residual DMAE, even at levels below choline plasma concentrations found during fasting, compromises [F-18]FCho uptake in vivo and care should be taken to avoid its interference in molecular imaging with [F-18]FCho.
Keywords
F-18-Choline, Dimethylaminoethanol, Choline transporters, Positron emission tomography, Tumour visualization, POSITRON-EMISSION-TOMOGRAPHY, CHOLINE ANALOGS, AUTOMATED SYNTHESIS, PROSTATE-CANCER, EMITTING TRACER, BREAST-CANCER, TRANSPORT, PET, CELLS, F-18-FLUOROCHOLINE

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Chicago
Slaets, Dominique, SYLVIE DE BRUYNE, Caroline Dumolyn, Lieselotte Moerman, Koen Mertens, and Filip De Vos. 2010. “Reduced Dimethylaminoethanol in [18F]fluoromethylcholine: An Important Step Towards Enhanced Tumour Visualization.” European Journal of Nuclear Medicine and Molecular Imaging 37 (11): 2136–2145.
APA
Slaets, D., DE BRUYNE, S., Dumolyn, C., Moerman, L., Mertens, K., & De Vos, F. (2010). Reduced dimethylaminoethanol in [18F]fluoromethylcholine: an important step towards enhanced tumour visualization. EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING, 37(11), 2136–2145.
Vancouver
1.
Slaets D, DE BRUYNE S, Dumolyn C, Moerman L, Mertens K, De Vos F. Reduced dimethylaminoethanol in [18F]fluoromethylcholine: an important step towards enhanced tumour visualization. EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING. 2010;37(11):2136–45.
MLA
Slaets, Dominique, SYLVIE DE BRUYNE, Caroline Dumolyn, et al. “Reduced Dimethylaminoethanol in [18F]fluoromethylcholine: An Important Step Towards Enhanced Tumour Visualization.” EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING 37.11 (2010): 2136–2145. Print.
@article{1234682,
  abstract     = {[F-18]Fluoromethylcholine ([F-18]FCho) is a radiotracer generally used for tumour visualization in patients. Due to high levels of dimethylaminoethanol (DMAE) remaining in [F-18]FCho solutions synthesized by currently available methods, tumour visualization might be compromised.
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 [F-18]FCho pharmacokinetics was further elaborated in a xenograft mouse model.
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) [F-18]FCho uptake was reduced in the presence of DMAE at concentrations above 0.5 A mu M and (2) DMAE is a competitive inhibitor of [F-18]FCho transport. In vivo experiments in xenograft mouse models corroborated reduced tumour uptake at DMAE plasma levels of about 2.5 A mu M as found in patients injected with contaminated [F-18]FCho.
Residual DMAE, even at levels below choline plasma concentrations found during fasting, compromises [F-18]FCho uptake in vivo and care should be taken to avoid its interference in molecular imaging with [F-18]FCho.},
  author       = {Slaets, Dominique and DE BRUYNE, SYLVIE and Dumolyn, Caroline and Moerman, Lieselotte and Mertens, Koen and De Vos, Filip},
  issn         = {1619-7070},
  journal      = {EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING},
  keyword      = {F-18-Choline,Dimethylaminoethanol,Choline transporters,Positron emission tomography,Tumour visualization,POSITRON-EMISSION-TOMOGRAPHY,CHOLINE ANALOGS,AUTOMATED SYNTHESIS,PROSTATE-CANCER,EMITTING TRACER,BREAST-CANCER,TRANSPORT,PET,CELLS,F-18-FLUOROCHOLINE},
  language     = {eng},
  number       = {11},
  pages        = {2136--2145},
  title        = {Reduced dimethylaminoethanol in [18F]fluoromethylcholine: an important step towards enhanced tumour visualization},
  url          = {http://dx.doi.org/10.1007/s00259-010-1508-z},
  volume       = {37},
  year         = {2010},
}

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