Journal article
Fluorine-18 and carbon-11 labeled amphetamine analogs—Synthesis, distribution, binding characteristics in mice and rats and a PET study in monkey
Nuclear medicine and biology, Vol.20(8), pp.973-981
1993
DOI: 10.1016/0969-8051(93)90098-F
PMID: 8298577
Abstract
No-carrier-added (NCA) (±)-
p-[
18F]fluoroamphetamine (
2a) and (±)-6-[
18F]fluoro-3,4-methylene-dioxyamphetamine (
2b) were synthesized through a multistep synthesis by nucleophilic substitution of the appropriate precursors (
p-nitrobenzaldehyde,
1a and 6-nitropiperonal
1b, respectively) with [
18F]fluoride followed by condensation with nitroethane and reduction with LAH in 20–30% yield (EOB) in a synthesis time of 90–109 min from EOB. NCA (−)-[
11C]methamphetamine (
4a) and (±)-3,4-methylenedioxy-
N-[
11C]methamphetamine (
4b) were synthesized by methylation of the appropriate desmethyl precursors
3a and
3b with [
11C]H
3I in 40–60% yield (EOB) in a synthesis time of 30 min from EOB. Animal studies in mouse and rat revealed that the relative tissue uptake of these radiotracers was kidneys > lungs > liver > spleen > brain > heart > blood. The uptakes of these radiotracers in mouse brain were high and similar at 5 min post-injection (approx. 5%/g) but radioactivity then declined rapidly (approx. 1%/g at 60 min post-injection). For compounds
2a and
2b, the activity in the femur did not increase with time indicating
in vivo defluorination may not be the major route of metabolism. Monoamine uptake inhibitors (nomifensine, fluoxetine and nisoxetine) did not inhibit but enhance the uptake of (−)-[
11C]methamphetamine (
4a) in the rat brain by greater than 50%. A PET study in a Rhesus monkey revealed that the uptakes of (−)-[
11C]methamphetamine in different brain regions were similar and the retention of the radioactivity in these regions remained constant throughout the study. Analysis of arterial plasma by HPLC showed that 50% of radioactivity remained as
4a at 60 min post-injection.
Details
- Title: Subtitle
- Fluorine-18 and carbon-11 labeled amphetamine analogs—Synthesis, distribution, binding characteristics in mice and rats and a PET study in monkey
- Creators
- Chyng-Yann ShiueGrace G Shiue - Center for Metabolic Imaging, Creighton University, 901 Dorcas Street, Omaha, NE 68108 U.S.AJoseph A Rysavy - Center for Metabolic Imaging, Creighton University, 901 Dorcas Street, Omaha, NE 68108 U.S.ARichard C Pleus - Department of Pharmacology University of Nebraska Medical Center, Omaha, NE 68198, U.S.AHui Huang - Center for Metabolic Imaging, Creighton University, 901 Dorcas Street, Omaha, NE 68108 U.S.ALan-Qin Bai - Center for Metabolic Imaging, Creighton University, 901 Dorcas Street, Omaha, NE 68108 U.S.AKurtis G Cornish - Department of Physiology, University of Nebraska Medical Center, Omaha, NE 68198, U.S.AJohn J Sunderland - Center for Metabolic Imaging, Creighton University, 901 Dorcas Street, Omaha, NE 68108 U.S.AMathis P Frick - Center for Metabolic Imaging, Creighton University, 901 Dorcas Street, Omaha, NE 68108 U.S.A
- Resource Type
- Journal article
- Publication Details
- Nuclear medicine and biology, Vol.20(8), pp.973-981
- Publisher
- Elsevier Inc
- DOI
- 10.1016/0969-8051(93)90098-F
- PMID
- 8298577
- ISSN
- 0969-8051
- eISSN
- 1872-9614
- Language
- English
- Date published
- 1993
- Academic Unit
- Radiology; Physics and Astronomy; Radiation Oncology
- Record Identifier
- 9984047675602771
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