Chemical fate of the nicotinic acetylcholinergic radiotracer [123I]5-IA-85380 in baboon brain and plasma

Ronald M. Baldwin; Sami S. Zoghbi; Julie K. Staley; Eric Brenner; Mohammed S. Al-Tikriti; Louis Amici; Masahiro Fujita; Robert B. Innis; Gilles Tamagnan

doi:10.1016/j.nucmedbio.2006.03.002

Chemical fate of the nicotinic acetylcholinergic radiotracer [¹²³I]5-IA-85380 in baboon brain and plasma

Ronald M. Baldwin, Sami S. Zoghbi, Julie K. Staley, Eric Brenner, Mohammed S. Al-Tikriti, Louis Amici, Masahiro Fujita, Robert B. Innis, Gilles Tamagnan

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

5 Scopus citations

Abstract

The fate of the nicotinic acetylcholinergic receptor radiotracer [¹²³I]5-IA-85380 ([¹²³I]5-IA) was studied in baboon by analyzing the chemical composition of brain tissue and plasma after intravenous administration of the tracer. Acetonitrile denaturation and high-performance liquid chromatography (HPLC) analysis showed predominantly unchanged (91-98%) parent tracer in all brain tissues examined, compared to significant metabolism (23% parent) in the plasma at 90 min postinjection, and control tissue recovery of 95-98%. [¹²³I]5-IA was distributed to the thalamus with a standardized uptake value of 9.2 (0.04% dose/g) or a concentration 5.8 times higher than that of the cerebellum. The HPLC behavior of a synthesized sample of one hypothesized metabolite, 5-iodo-3-pyridinol (5-IP), was consistent with plasma radiometabolite fraction. Since only parent radiotracer compound was found in brain tissue, these results add confidence that information derived from single photon emission computed tomography images of ¹²³I activity in the brain after [¹²³I]5-IA administration can be interpreted as distribution of an intact radiotracer.

Original language	English (US)
Pages (from-to)	549-554
Number of pages	6
Journal	Nuclear Medicine and Biology
Volume	33
Issue number	4
DOIs	https://doi.org/10.1016/j.nucmedbio.2006.03.002
State	Published - May 2006

Keywords

(S)-5-[I]iodo-3-(2-azetidinylmethoxy)pyridine
5-iodo-3-pyridinol
Metabolites
Nicotinic acetylcholine receptor
Pharmacokinetics
SPECT tracer validation
[I]5-IA-85380

ASJC Scopus subject areas

Molecular Medicine
Radiology Nuclear Medicine and imaging
Cancer Research

Access to Document

10.1016/j.nucmedbio.2006.03.002

Cite this

@article{4e10220724544c408a4f5f61ec9de1a3,

title = "Chemical fate of the nicotinic acetylcholinergic radiotracer [123I]5-IA-85380 in baboon brain and plasma",

abstract = "The fate of the nicotinic acetylcholinergic receptor radiotracer [123I]5-IA-85380 ([123I]5-IA) was studied in baboon by analyzing the chemical composition of brain tissue and plasma after intravenous administration of the tracer. Acetonitrile denaturation and high-performance liquid chromatography (HPLC) analysis showed predominantly unchanged (91-98%) parent tracer in all brain tissues examined, compared to significant metabolism (23% parent) in the plasma at 90 min postinjection, and control tissue recovery of 95-98%. [123I]5-IA was distributed to the thalamus with a standardized uptake value of 9.2 (0.04% dose/g) or a concentration 5.8 times higher than that of the cerebellum. The HPLC behavior of a synthesized sample of one hypothesized metabolite, 5-iodo-3-pyridinol (5-IP), was consistent with plasma radiometabolite fraction. Since only parent radiotracer compound was found in brain tissue, these results add confidence that information derived from single photon emission computed tomography images of 123I activity in the brain after [123I]5-IA administration can be interpreted as distribution of an intact radiotracer.",

keywords = "(S)-5-[I]iodo-3-(2-azetidinylmethoxy)pyridine, 5-iodo-3-pyridinol, Metabolites, Nicotinic acetylcholine receptor, Pharmacokinetics, SPECT tracer validation, [I]5-IA-85380",

author = "Baldwin, {Ronald M.} and Zoghbi, {Sami S.} and Staley, {Julie K.} and Eric Brenner and Al-Tikriti, {Mohammed S.} and Louis Amici and Masahiro Fujita and Innis, {Robert B.} and Gilles Tamagnan",

note = "Funding Information: The authors gratefully acknowledge the assistance of Nina Sheung with radiochemistry and Shawna Ellis with animal imaging. This work was supported, in part, by the NIDA/NCI Transdisciplinary Tobacco Use Research Center (P50 DA84733), the NIH GCRC (MO1-RR00125) and the Veterans Affairs Research Enhancement Award Program (REAP) Center on “Neural Mechanisms and Treatment Response in Depression.” Copyright: Copyright 2008 Elsevier B.V., All rights reserved.",

year = "2006",

month = may,

doi = "10.1016/j.nucmedbio.2006.03.002",

language = "English (US)",

volume = "33",

pages = "549--554",

journal = "Nuclear Medicine and Biology",

issn = "0969-8051",

publisher = "Elsevier",

number = "4",

}

TY - JOUR

T1 - Chemical fate of the nicotinic acetylcholinergic radiotracer [123I]5-IA-85380 in baboon brain and plasma

AU - Baldwin, Ronald M.

AU - Zoghbi, Sami S.

AU - Staley, Julie K.

AU - Brenner, Eric

AU - Al-Tikriti, Mohammed S.

AU - Amici, Louis

AU - Fujita, Masahiro

AU - Innis, Robert B.

AU - Tamagnan, Gilles

N1 - Funding Information: The authors gratefully acknowledge the assistance of Nina Sheung with radiochemistry and Shawna Ellis with animal imaging. This work was supported, in part, by the NIDA/NCI Transdisciplinary Tobacco Use Research Center (P50 DA84733), the NIH GCRC (MO1-RR00125) and the Veterans Affairs Research Enhancement Award Program (REAP) Center on “Neural Mechanisms and Treatment Response in Depression.” Copyright: Copyright 2008 Elsevier B.V., All rights reserved.

PY - 2006/5

Y1 - 2006/5

N2 - The fate of the nicotinic acetylcholinergic receptor radiotracer [123I]5-IA-85380 ([123I]5-IA) was studied in baboon by analyzing the chemical composition of brain tissue and plasma after intravenous administration of the tracer. Acetonitrile denaturation and high-performance liquid chromatography (HPLC) analysis showed predominantly unchanged (91-98%) parent tracer in all brain tissues examined, compared to significant metabolism (23% parent) in the plasma at 90 min postinjection, and control tissue recovery of 95-98%. [123I]5-IA was distributed to the thalamus with a standardized uptake value of 9.2 (0.04% dose/g) or a concentration 5.8 times higher than that of the cerebellum. The HPLC behavior of a synthesized sample of one hypothesized metabolite, 5-iodo-3-pyridinol (5-IP), was consistent with plasma radiometabolite fraction. Since only parent radiotracer compound was found in brain tissue, these results add confidence that information derived from single photon emission computed tomography images of 123I activity in the brain after [123I]5-IA administration can be interpreted as distribution of an intact radiotracer.

AB - The fate of the nicotinic acetylcholinergic receptor radiotracer [123I]5-IA-85380 ([123I]5-IA) was studied in baboon by analyzing the chemical composition of brain tissue and plasma after intravenous administration of the tracer. Acetonitrile denaturation and high-performance liquid chromatography (HPLC) analysis showed predominantly unchanged (91-98%) parent tracer in all brain tissues examined, compared to significant metabolism (23% parent) in the plasma at 90 min postinjection, and control tissue recovery of 95-98%. [123I]5-IA was distributed to the thalamus with a standardized uptake value of 9.2 (0.04% dose/g) or a concentration 5.8 times higher than that of the cerebellum. The HPLC behavior of a synthesized sample of one hypothesized metabolite, 5-iodo-3-pyridinol (5-IP), was consistent with plasma radiometabolite fraction. Since only parent radiotracer compound was found in brain tissue, these results add confidence that information derived from single photon emission computed tomography images of 123I activity in the brain after [123I]5-IA administration can be interpreted as distribution of an intact radiotracer.

KW - (S)-5-[I]iodo-3-(2-azetidinylmethoxy)pyridine

KW - 5-iodo-3-pyridinol

KW - Metabolites

KW - Nicotinic acetylcholine receptor

KW - Pharmacokinetics

KW - SPECT tracer validation

KW - [I]5-IA-85380

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UR - http://www.scopus.com/inward/citedby.url?scp=33646542645&partnerID=8YFLogxK

U2 - 10.1016/j.nucmedbio.2006.03.002

DO - 10.1016/j.nucmedbio.2006.03.002

M3 - Article

C2 - 16720248

AN - SCOPUS:33646542645

VL - 33

SP - 549

EP - 554

JO - Nuclear Medicine and Biology

JF - Nuclear Medicine and Biology

SN - 0969-8051

IS - 4

ER -