Fluorine-18 and carbon-11 labeled amphetamine analogs-Synthesis, distribution, binding characteristics in mice and rats and a PET study in monkey

Chyng Yann Shiue, Grace G. Shiue, Joseph A. Rysavy, Richard C. Pleus, Hui Huang, Lan Qin Bai, Kurtis G Cornish, John J. Sunderland, Mathis P. Frick

Research output: Contribution to journalArticle

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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]H3I 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.

Original languageEnglish (US)
Pages (from-to)973-981
Number of pages9
JournalNuclear Medicine and Biology
Volume20
Issue number8
DOIs
StatePublished - Jan 1 1993

Fingerprint

Methamphetamine
Fluorine
Amphetamine
Haplorhini
Carbon
Radioactivity
nisoxetine
Brain
Injections
Nomifensine
Fluoxetine
Macaca mulatta
Fluorides
Femur
Methylation
Spleen
High Pressure Liquid Chromatography
Kidney
Lung
Liver

ASJC Scopus subject areas

  • Molecular Medicine
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

Cite this

Fluorine-18 and carbon-11 labeled amphetamine analogs-Synthesis, distribution, binding characteristics in mice and rats and a PET study in monkey. / Shiue, Chyng Yann; Shiue, Grace G.; Rysavy, Joseph A.; Pleus, Richard C.; Huang, Hui; Bai, Lan Qin; Cornish, Kurtis G; Sunderland, John J.; Frick, Mathis P.

In: Nuclear Medicine and Biology, Vol. 20, No. 8, 01.01.1993, p. 973-981.

Research output: Contribution to journalArticle

Shiue, CY, Shiue, GG, Rysavy, JA, Pleus, RC, Huang, H, Bai, LQ, Cornish, KG, Sunderland, JJ & Frick, MP 1993, '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, no. 8, pp. 973-981. https://doi.org/10.1016/0969-8051(93)90098-F
Shiue, Chyng Yann ; Shiue, Grace G. ; Rysavy, Joseph A. ; Pleus, Richard C. ; Huang, Hui ; Bai, Lan Qin ; Cornish, Kurtis G ; Sunderland, John J. ; Frick, Mathis P. / Fluorine-18 and carbon-11 labeled amphetamine analogs-Synthesis, distribution, binding characteristics in mice and rats and a PET study in monkey. In: Nuclear Medicine and Biology. 1993 ; Vol. 20, No. 8. pp. 973-981.
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