Synthesis and preliminary evaluation of [11C]NE-100 labeled in two different positions as a PET σ receptor ligand

Kiichi Ishiwata, Junko Noguchi, Shin Ichi Ishii, Kentaro Hatano, Kengo Ito, Toshitaka Nabeshima, Michio Senda

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

N,N-Dipropyl-2-[4-methoxy-3-(2-phenylethoxy)phenyl]ethylamine (NE-100) was labeled with 11C in two different positions by the alkylation of an N- despropyl precursor with [11C]propyl iodide and of an O-desmethyl precursor with [11C]methyl iodide and was evaluated for the potential as a tracer for mapping σ 1 receptors in the CNS and peripheral organs by PET. Following i.v. injection of [N-propyl-11C]NE-100 or [O-methyl-11C]NE-100 into mice, the two tracers showed similar tissue distribution patterns except for the liver and brain. With the coinjected carrier NE-100 or haloperidol, the uptake of [N-propyl-11C]NE-100 by the liver, pancreas and spleen was significantly decreased at 15 min after injection, whereas the effect was not significant for [O-methyl-11C]NE-100. The coinjection of NE-100 enhanced the brain uptake of the two tracers. Haloperidol also enhanced the brain uptake of [N-propyl-11C]NE-100, but not that of [O-methyl-11C]NE-100. The regional brain distribution assessed with [O-methyl-3H]NE-100 was consistent with the distribution pattern of the σ receptors. Four σ drugs reduced the regional brain uptake of [O-methyl-3H]NE-100 to 70%-90% of the control. In an ex vivo autoradiographic study of the rat brain, the uptake of [O-methyl- 11C]NE-100 was blocked by carrier NE-100 or haloperidol (53%-59% of the control in the cortex), which suggests a receptor-specific distribution. These results show that [O-methyl-11C]NE-100 has limited potential as a PET ligand for mapping σ 1 receptors in the peripheral organs and the CNS because of high nonspecific binding.

Original languageEnglish
Pages (from-to)195-202
Number of pages8
JournalNuclear Medicine and Biology
Volume25
Issue number3
DOIs
Publication statusPublished - 01-04-1998
Externally publishedYes

Fingerprint

Ligands
Brain
Haloperidol
N,N-dipropyl-2-(4-methoxy-3-(2-phenylethoxy)phenyl)ethylamine monohydrochloride
Injections
Liver
Alkylation
Tissue Distribution
Pancreas
Spleen

All Science Journal Classification (ASJC) codes

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

Cite this

Ishiwata, Kiichi ; Noguchi, Junko ; Ishii, Shin Ichi ; Hatano, Kentaro ; Ito, Kengo ; Nabeshima, Toshitaka ; Senda, Michio. / Synthesis and preliminary evaluation of [11C]NE-100 labeled in two different positions as a PET σ receptor ligand. In: Nuclear Medicine and Biology. 1998 ; Vol. 25, No. 3. pp. 195-202.
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abstract = "N,N-Dipropyl-2-[4-methoxy-3-(2-phenylethoxy)phenyl]ethylamine (NE-100) was labeled with 11C in two different positions by the alkylation of an N- despropyl precursor with [11C]propyl iodide and of an O-desmethyl precursor with [11C]methyl iodide and was evaluated for the potential as a tracer for mapping σ 1 receptors in the CNS and peripheral organs by PET. Following i.v. injection of [N-propyl-11C]NE-100 or [O-methyl-11C]NE-100 into mice, the two tracers showed similar tissue distribution patterns except for the liver and brain. With the coinjected carrier NE-100 or haloperidol, the uptake of [N-propyl-11C]NE-100 by the liver, pancreas and spleen was significantly decreased at 15 min after injection, whereas the effect was not significant for [O-methyl-11C]NE-100. The coinjection of NE-100 enhanced the brain uptake of the two tracers. Haloperidol also enhanced the brain uptake of [N-propyl-11C]NE-100, but not that of [O-methyl-11C]NE-100. The regional brain distribution assessed with [O-methyl-3H]NE-100 was consistent with the distribution pattern of the σ receptors. Four σ drugs reduced the regional brain uptake of [O-methyl-3H]NE-100 to 70{\%}-90{\%} of the control. In an ex vivo autoradiographic study of the rat brain, the uptake of [O-methyl- 11C]NE-100 was blocked by carrier NE-100 or haloperidol (53{\%}-59{\%} of the control in the cortex), which suggests a receptor-specific distribution. These results show that [O-methyl-11C]NE-100 has limited potential as a PET ligand for mapping σ 1 receptors in the peripheral organs and the CNS because of high nonspecific binding.",
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Synthesis and preliminary evaluation of [11C]NE-100 labeled in two different positions as a PET σ receptor ligand. / Ishiwata, Kiichi; Noguchi, Junko; Ishii, Shin Ichi; Hatano, Kentaro; Ito, Kengo; Nabeshima, Toshitaka; Senda, Michio.

In: Nuclear Medicine and Biology, Vol. 25, No. 3, 01.04.1998, p. 195-202.

Research output: Contribution to journalArticle

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T1 - Synthesis and preliminary evaluation of [11C]NE-100 labeled in two different positions as a PET σ receptor ligand

AU - Ishiwata, Kiichi

AU - Noguchi, Junko

AU - Ishii, Shin Ichi

AU - Hatano, Kentaro

AU - Ito, Kengo

AU - Nabeshima, Toshitaka

AU - Senda, Michio

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AB - N,N-Dipropyl-2-[4-methoxy-3-(2-phenylethoxy)phenyl]ethylamine (NE-100) was labeled with 11C in two different positions by the alkylation of an N- despropyl precursor with [11C]propyl iodide and of an O-desmethyl precursor with [11C]methyl iodide and was evaluated for the potential as a tracer for mapping σ 1 receptors in the CNS and peripheral organs by PET. Following i.v. injection of [N-propyl-11C]NE-100 or [O-methyl-11C]NE-100 into mice, the two tracers showed similar tissue distribution patterns except for the liver and brain. With the coinjected carrier NE-100 or haloperidol, the uptake of [N-propyl-11C]NE-100 by the liver, pancreas and spleen was significantly decreased at 15 min after injection, whereas the effect was not significant for [O-methyl-11C]NE-100. The coinjection of NE-100 enhanced the brain uptake of the two tracers. Haloperidol also enhanced the brain uptake of [N-propyl-11C]NE-100, but not that of [O-methyl-11C]NE-100. The regional brain distribution assessed with [O-methyl-3H]NE-100 was consistent with the distribution pattern of the σ receptors. Four σ drugs reduced the regional brain uptake of [O-methyl-3H]NE-100 to 70%-90% of the control. In an ex vivo autoradiographic study of the rat brain, the uptake of [O-methyl- 11C]NE-100 was blocked by carrier NE-100 or haloperidol (53%-59% of the control in the cortex), which suggests a receptor-specific distribution. These results show that [O-methyl-11C]NE-100 has limited potential as a PET ligand for mapping σ 1 receptors in the peripheral organs and the CNS because of high nonspecific binding.

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