| Effect of vehicle on brain uptake of [11C]toluene. | |
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MedLine Citation:
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PMID: 12088732 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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With the goal of investigating the pharmacokinetics of the abused solvent, toluene we have adapted the rapid coupling of methyl iodide with tributylphenylstannane mediated by palladium(0) complex to the synthesis of no-carrier-added [11C]toluene starting with 11CH(3)I. Two methods for purification and formulation of the tracer were developed. The first one yielded [11C]toluene dissolved in dimethylacetamide/saline solution, for the second one we adapted supercritical fluid technology where the tracer was purified using and conventional C(18) HPLC column and pure supercritical CO(2) fluid as a mobile phase operating at 2000 psi. Formulation of the tracer in cyclodextrin resulted in a significantly higher integrated uptake and distribution volume values. Additionally, we observed higher uptake and slower clearance of 11C-toluene in white matter, consistent with higher lipid content and neurotoxicological evidence indicating restricted and diffuse white matter changes in toluene abusers. This trend was observed when either DMA or cyclodextrin was used as a vehicle. It appears then, that the choice of a vehicle affected only the degree of bioavailability, but not the regional brain pharmacokinetics. Finally, we demonstrated the effect of a decreased percent difference between DV values for the studies performed on the same day, that is, test/retest variability was lower for all brain regions in beta-cyclodextrin experiments. Present results clearly demonstrate that the choice of a vehicle has a significant effect on tracer uptake and should be considered as a potential factor contributing to the pharmacokinetic measurements. |
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Authors:
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Madina R Gerasimov; Jean Logan; Richard A Ferrieri; Ryan D Muller; David Alexoff; Stephen L Dewey |
Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, U.S. Gov't, Non-P.H.S. |
Journal Detail:
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Title: Nuclear medicine and biology Volume: 29 ISSN: 0969-8051 ISO Abbreviation: Nucl. Med. Biol. Publication Date: 2002 Jul |
Date Detail:
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Created Date: 2002-06-28 Completed Date: 2003-02-10 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 9304420 Medline TA: Nucl Med Biol Country: England |
Other Details:
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Languages: eng Pagination: 607-12 Citation Subset: IM |
Affiliation:
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Brookhaven National Laboratory, Department of Chemistry, Upton, NY 11973, USA. madina@bnl.gov |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Acetamides
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pharmacology Animals Brain / metabolism*, radionuclide imaging Carbon Radioisotopes / diagnostic use, isolation & purification, pharmacokinetics* Cyclodextrins / pharmacology* Female Isotope Labeling / methods* Papio Radiopharmaceuticals / chemical synthesis, diagnostic use, pharmacokinetics Tissue Distribution Toluene / diagnostic use, pharmacokinetics* Vehicles / pharmacology |
| Chemical | |
Reg. No./Substance:
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0/Acetamides; 0/Carbon Radioisotopes; 0/Cyclodextrins; 0/Radiopharmaceuticals; 0/Vehicles; 108-88-3/Toluene; 127-19-5/dimethylacetamide |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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