Radiosynthesis and mouse brain distribution studies of [11C] CP-126,998: A PET ligand for In vivo study of acetylcholinesterase

John L. Musachio; John E. Flesher; Ursula A. Scheffel; Paige Rauseo; John Hilton; William B. Mathews; Hayden T. Ravert; Robert F. Dannals; J. James Frost

doi:10.1016/S0969-8051(02)00299-8

Radiosynthesis and mouse brain distribution studies of [¹¹C] CP-126,998: A PET ligand for In vivo study of acetylcholinesterase

John L. Musachio, John E. Flesher, Ursula A. Scheffel, Paige Rauseo, John Hilton, William B. Mathews, Hayden T. Ravert, Robert F. Dannals, J. James Frost

School of Medicine

Research output: Contribution to journal › Article › peer-review

20 Scopus citations

Abstract

The selective, reversible acetylcholinesterase inhibitor 5,7-Dihydro-7-methyl-3- [2-[1-(phenylmethyl]-4-piperidinyl]ethyl]-6H-pyrrolo[3,2-f]-1, 2-benzisoxazol3-6-one (CP-126,998) was labeled with C-11 iodomethane via base-promoted alkylation of the lactam nitrogen. [¹¹C] CP-126,998 was synthesized in good radiochemical yield (13-29% non-decay corrected) and high specific radioactivity (177-418 GBq/μmol). In vivo mouse biodistribution studies reveal [¹¹C] CP-126,998 to localize preferentially in striatal tissue, a region known to be rich in acetylcholinesterase. Competitive blocking studies using a variety of acetylcholinesterase inhibitors (diisopropylfluorophosphate, tacrine, CP-118,954) verified the specificity of the PET radiotracer for brain acetylcholinesterase.

Original language	English (US)
Pages (from-to)	547-552
Number of pages	6
Journal	Nuclear Medicine and Biology
Volume	29
Issue number	5
DOIs	https://doi.org/10.1016/S0969-8051(02)00299-8
State	Published - 2002

Keywords

Acetylcholinesterase
Alzheimer's disease
C-11
Diisopropylfluorophosphate
PET

ASJC Scopus subject areas

Molecular Medicine
Radiology Nuclear Medicine and imaging
Cancer Research

Access to Document

10.1016/S0969-8051(02)00299-8

Cite this

@article{389e51439b634aa6ba075c54918ec5df,

title = "Radiosynthesis and mouse brain distribution studies of [11C] CP-126,998: A PET ligand for In vivo study of acetylcholinesterase",

abstract = "The selective, reversible acetylcholinesterase inhibitor 5,7-Dihydro-7-methyl-3- [2-[1-(phenylmethyl]-4-piperidinyl]ethyl]-6H-pyrrolo[3,2-f]-1, 2-benzisoxazol3-6-one (CP-126,998) was labeled with C-11 iodomethane via base-promoted alkylation of the lactam nitrogen. [11C] CP-126,998 was synthesized in good radiochemical yield (13-29% non-decay corrected) and high specific radioactivity (177-418 GBq/μmol). In vivo mouse biodistribution studies reveal [11C] CP-126,998 to localize preferentially in striatal tissue, a region known to be rich in acetylcholinesterase. Competitive blocking studies using a variety of acetylcholinesterase inhibitors (diisopropylfluorophosphate, tacrine, CP-118,954) verified the specificity of the PET radiotracer for brain acetylcholinesterase.",

keywords = "Acetylcholinesterase, Alzheimer's disease, C-11, Diisopropylfluorophosphate, PET",

author = "Musachio, {John L.} and Flesher, {John E.} and Scheffel, {Ursula A.} and Paige Rauseo and John Hilton and Mathews, {William B.} and Ravert, {Hayden T.} and Dannals, {Robert F.} and {James Frost}, J.",

year = "2002",

doi = "10.1016/S0969-8051(02)00299-8",

language = "English (US)",

volume = "29",

pages = "547--552",

journal = "Nuclear Medicine and Biology",

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T2 - A PET ligand for In vivo study of acetylcholinesterase

AU - Musachio, John L.

AU - Flesher, John E.

AU - Scheffel, Ursula A.

AU - Rauseo, Paige

AU - Hilton, John

AU - Mathews, William B.

AU - Ravert, Hayden T.

AU - Dannals, Robert F.

AU - James Frost, J.

PY - 2002

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N2 - The selective, reversible acetylcholinesterase inhibitor 5,7-Dihydro-7-methyl-3- [2-[1-(phenylmethyl]-4-piperidinyl]ethyl]-6H-pyrrolo[3,2-f]-1, 2-benzisoxazol3-6-one (CP-126,998) was labeled with C-11 iodomethane via base-promoted alkylation of the lactam nitrogen. [11C] CP-126,998 was synthesized in good radiochemical yield (13-29% non-decay corrected) and high specific radioactivity (177-418 GBq/μmol). In vivo mouse biodistribution studies reveal [11C] CP-126,998 to localize preferentially in striatal tissue, a region known to be rich in acetylcholinesterase. Competitive blocking studies using a variety of acetylcholinesterase inhibitors (diisopropylfluorophosphate, tacrine, CP-118,954) verified the specificity of the PET radiotracer for brain acetylcholinesterase.

AB - The selective, reversible acetylcholinesterase inhibitor 5,7-Dihydro-7-methyl-3- [2-[1-(phenylmethyl]-4-piperidinyl]ethyl]-6H-pyrrolo[3,2-f]-1, 2-benzisoxazol3-6-one (CP-126,998) was labeled with C-11 iodomethane via base-promoted alkylation of the lactam nitrogen. [11C] CP-126,998 was synthesized in good radiochemical yield (13-29% non-decay corrected) and high specific radioactivity (177-418 GBq/μmol). In vivo mouse biodistribution studies reveal [11C] CP-126,998 to localize preferentially in striatal tissue, a region known to be rich in acetylcholinesterase. Competitive blocking studies using a variety of acetylcholinesterase inhibitors (diisopropylfluorophosphate, tacrine, CP-118,954) verified the specificity of the PET radiotracer for brain acetylcholinesterase.

KW - Acetylcholinesterase

KW - Alzheimer's disease

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KW - Diisopropylfluorophosphate

KW - PET

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