Synthesis and initial PET imaging of new potential NK1 receptor radioligands 1-[2-(3,5-bis-trifluoromethyl-benzyloxy)-1-phenyl-ethyl]-4-[ 11C]methyl-piperazine and {4-[2-(3,5-bis-trifluoromethyl-benzyloxy)- 1-phenyl-ethyl]-piperazine-1-yl}-acetic acid [11C]methyl ester

Mingzhang Gao, Bruce H. Mock, Gary Hutchins, Qi-Huang Zheng

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19 Citations (Scopus)

Abstract

The NK1 receptor radioligands 1-[2-(3,5-bis-trifluoromethyl- benzyloxy)-1-phenyl-ethyl]-4-[11C]methyl-piperazine ([ 11C]BMP, [11C]1) and {4-[2-(3,5-bis-trifluoromethyl- benzyloxy)-1-phenyl-ethyl]-piperazine-1-yl}-acetic acid [11C]methyl ester ([11C]BME, [11C]2) were synthesized for evaluation as new potential PET imaging agents for brain NK1 receptors. The new tracers [11C]BMP and [11C]BME were prepared by N-[ 11C]methylation and O-[11C]methylation of corresponding precursors 1-[2-(3,5-bis-trifluoromethyl-benzyloxy)-1-phenyl-ethyl]-piperazine and {4-[2-(3,5-bis-trifluoromethyl-benzyloxy)-1-phenyl-ethyl]-piperazine-1-yl}- acetic acid using [11C]methyl triflate and isolated by solid-phase extraction (SPE) purification procedure with 40-55% radiochemical yields, decay corrected to end of bombardment, and a synthesis time of 15-20 min. The initial PET dynamic studies of the tracers [11C]1 and [11C]2 in rats were performed using an animal PET scanner, IndyPET-II, developed in our laboratory. The results show the tracer [11C]BMP had better uptake in the animal brain than the tracer [11C]BME and gave higher quality rat brain images. Blocking studies by intravenous coinjection of hot tracer [11C]BMP with cold drug BMP had no effect on [11C]BMP-PET rat brain imaging. Likewise, blocking studies by intravenous coinjection of hot tracer [11C]BME with cold drug BME also showed no effect on [ 11C]BME-PET rat brain imaging. These results suggest that the localization of [11C]BMP and [11C]BME in rat brain is mediated by nonspecific processes, and the visualization of [ 11C]BMP-PET and [11C]BME-PET on rat brain is related to nonspecific binding.

Original languageEnglish
Pages (from-to)543-552
Number of pages10
JournalNuclear Medicine and Biology
Volume32
Issue number5
DOIs
StatePublished - Jul 2005

Fingerprint

Neuroimaging
Brain
Methylation
Solid Phase Extraction
Acetic Acid
Pharmaceutical Preparations
piperazine
methyl acetate
2-methyl piperazine
methyl triflate

Keywords

  • 1-[2-(3,5-Bis-trifluoromethyl-benzyloxy)-1-phenyl-ethyl]-4-[ C]methyl-piperazine
  • Brain
  • Positron emission tomography
  • {4-[2-(3,5-Bis-trifluoromethyl-benzyloxy)-1- phenyl-ethyl]-piperazine-1-yl}-acetic acid [C]methyl ester

ASJC Scopus subject areas

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

Cite this

@article{30cfb4f66fb5421e8e1d19bbbb949b57,
title = "Synthesis and initial PET imaging of new potential NK1 receptor radioligands 1-[2-(3,5-bis-trifluoromethyl-benzyloxy)-1-phenyl-ethyl]-4-[ 11C]methyl-piperazine and {4-[2-(3,5-bis-trifluoromethyl-benzyloxy)- 1-phenyl-ethyl]-piperazine-1-yl}-acetic acid [11C]methyl ester",
abstract = "The NK1 receptor radioligands 1-[2-(3,5-bis-trifluoromethyl- benzyloxy)-1-phenyl-ethyl]-4-[11C]methyl-piperazine ([ 11C]BMP, [11C]1) and {4-[2-(3,5-bis-trifluoromethyl- benzyloxy)-1-phenyl-ethyl]-piperazine-1-yl}-acetic acid [11C]methyl ester ([11C]BME, [11C]2) were synthesized for evaluation as new potential PET imaging agents for brain NK1 receptors. The new tracers [11C]BMP and [11C]BME were prepared by N-[ 11C]methylation and O-[11C]methylation of corresponding precursors 1-[2-(3,5-bis-trifluoromethyl-benzyloxy)-1-phenyl-ethyl]-piperazine and {4-[2-(3,5-bis-trifluoromethyl-benzyloxy)-1-phenyl-ethyl]-piperazine-1-yl}- acetic acid using [11C]methyl triflate and isolated by solid-phase extraction (SPE) purification procedure with 40-55{\%} radiochemical yields, decay corrected to end of bombardment, and a synthesis time of 15-20 min. The initial PET dynamic studies of the tracers [11C]1 and [11C]2 in rats were performed using an animal PET scanner, IndyPET-II, developed in our laboratory. The results show the tracer [11C]BMP had better uptake in the animal brain than the tracer [11C]BME and gave higher quality rat brain images. Blocking studies by intravenous coinjection of hot tracer [11C]BMP with cold drug BMP had no effect on [11C]BMP-PET rat brain imaging. Likewise, blocking studies by intravenous coinjection of hot tracer [11C]BME with cold drug BME also showed no effect on [ 11C]BME-PET rat brain imaging. These results suggest that the localization of [11C]BMP and [11C]BME in rat brain is mediated by nonspecific processes, and the visualization of [ 11C]BMP-PET and [11C]BME-PET on rat brain is related to nonspecific binding.",
keywords = "1-[2-(3,5-Bis-trifluoromethyl-benzyloxy)-1-phenyl-ethyl]-4-[ C]methyl-piperazine, Brain, Positron emission tomography, {4-[2-(3,5-Bis-trifluoromethyl-benzyloxy)-1- phenyl-ethyl]-piperazine-1-yl}-acetic acid [C]methyl ester",
author = "Mingzhang Gao and Mock, {Bruce H.} and Gary Hutchins and Qi-Huang Zheng",
year = "2005",
month = "7",
doi = "10.1016/j.nucmedbio.2005.03.012",
language = "English",
volume = "32",
pages = "543--552",
journal = "Nuclear Medicine and Biology",
issn = "0969-8051",
publisher = "Elsevier Inc.",
number = "5",

}

TY - JOUR

T1 - Synthesis and initial PET imaging of new potential NK1 receptor radioligands 1-[2-(3,5-bis-trifluoromethyl-benzyloxy)-1-phenyl-ethyl]-4-[ 11C]methyl-piperazine and {4-[2-(3,5-bis-trifluoromethyl-benzyloxy)- 1-phenyl-ethyl]-piperazine-1-yl}-acetic acid [11C]methyl ester

AU - Gao, Mingzhang

AU - Mock, Bruce H.

AU - Hutchins, Gary

AU - Zheng, Qi-Huang

PY - 2005/7

Y1 - 2005/7

N2 - The NK1 receptor radioligands 1-[2-(3,5-bis-trifluoromethyl- benzyloxy)-1-phenyl-ethyl]-4-[11C]methyl-piperazine ([ 11C]BMP, [11C]1) and {4-[2-(3,5-bis-trifluoromethyl- benzyloxy)-1-phenyl-ethyl]-piperazine-1-yl}-acetic acid [11C]methyl ester ([11C]BME, [11C]2) were synthesized for evaluation as new potential PET imaging agents for brain NK1 receptors. The new tracers [11C]BMP and [11C]BME were prepared by N-[ 11C]methylation and O-[11C]methylation of corresponding precursors 1-[2-(3,5-bis-trifluoromethyl-benzyloxy)-1-phenyl-ethyl]-piperazine and {4-[2-(3,5-bis-trifluoromethyl-benzyloxy)-1-phenyl-ethyl]-piperazine-1-yl}- acetic acid using [11C]methyl triflate and isolated by solid-phase extraction (SPE) purification procedure with 40-55% radiochemical yields, decay corrected to end of bombardment, and a synthesis time of 15-20 min. The initial PET dynamic studies of the tracers [11C]1 and [11C]2 in rats were performed using an animal PET scanner, IndyPET-II, developed in our laboratory. The results show the tracer [11C]BMP had better uptake in the animal brain than the tracer [11C]BME and gave higher quality rat brain images. Blocking studies by intravenous coinjection of hot tracer [11C]BMP with cold drug BMP had no effect on [11C]BMP-PET rat brain imaging. Likewise, blocking studies by intravenous coinjection of hot tracer [11C]BME with cold drug BME also showed no effect on [ 11C]BME-PET rat brain imaging. These results suggest that the localization of [11C]BMP and [11C]BME in rat brain is mediated by nonspecific processes, and the visualization of [ 11C]BMP-PET and [11C]BME-PET on rat brain is related to nonspecific binding.

AB - The NK1 receptor radioligands 1-[2-(3,5-bis-trifluoromethyl- benzyloxy)-1-phenyl-ethyl]-4-[11C]methyl-piperazine ([ 11C]BMP, [11C]1) and {4-[2-(3,5-bis-trifluoromethyl- benzyloxy)-1-phenyl-ethyl]-piperazine-1-yl}-acetic acid [11C]methyl ester ([11C]BME, [11C]2) were synthesized for evaluation as new potential PET imaging agents for brain NK1 receptors. The new tracers [11C]BMP and [11C]BME were prepared by N-[ 11C]methylation and O-[11C]methylation of corresponding precursors 1-[2-(3,5-bis-trifluoromethyl-benzyloxy)-1-phenyl-ethyl]-piperazine and {4-[2-(3,5-bis-trifluoromethyl-benzyloxy)-1-phenyl-ethyl]-piperazine-1-yl}- acetic acid using [11C]methyl triflate and isolated by solid-phase extraction (SPE) purification procedure with 40-55% radiochemical yields, decay corrected to end of bombardment, and a synthesis time of 15-20 min. The initial PET dynamic studies of the tracers [11C]1 and [11C]2 in rats were performed using an animal PET scanner, IndyPET-II, developed in our laboratory. The results show the tracer [11C]BMP had better uptake in the animal brain than the tracer [11C]BME and gave higher quality rat brain images. Blocking studies by intravenous coinjection of hot tracer [11C]BMP with cold drug BMP had no effect on [11C]BMP-PET rat brain imaging. Likewise, blocking studies by intravenous coinjection of hot tracer [11C]BME with cold drug BME also showed no effect on [ 11C]BME-PET rat brain imaging. These results suggest that the localization of [11C]BMP and [11C]BME in rat brain is mediated by nonspecific processes, and the visualization of [ 11C]BMP-PET and [11C]BME-PET on rat brain is related to nonspecific binding.

KW - 1-[2-(3,5-Bis-trifluoromethyl-benzyloxy)-1-phenyl-ethyl]-4-[ C]methyl-piperazine

KW - Brain

KW - Positron emission tomography

KW - {4-[2-(3,5-Bis-trifluoromethyl-benzyloxy)-1- phenyl-ethyl]-piperazine-1-yl}-acetic acid [C]methyl ester

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U2 - 10.1016/j.nucmedbio.2005.03.012

DO - 10.1016/j.nucmedbio.2005.03.012

M3 - Article

VL - 32

SP - 543

EP - 552

JO - Nuclear Medicine and Biology

JF - Nuclear Medicine and Biology

SN - 0969-8051

IS - 5

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