Ex vivo evaluation of N-(3-[18F]fluoropropyl)-2 beta-carbomethoxy-3 beta-(4-fluorophenyl)nortropane in rats

Teija Koivula; Päivi Marjamäki; Merja Haaparanta; Veronica Fagerholm; Tove Grönroos; Tiina Lipponen; Outi Perhola; Jouko Vepsäläinen; Olof Solin

doi:10.1016/j.nucmedbio.2007.09.006

Ex vivo evaluation of N-(3-[18F]fluoropropyl)-2 beta-carbomethoxy-3 beta-(4-fluorophenyl)nortropane in rats

Teija Koivula, Päivi Marjamäki, Merja Haaparanta, Veronica Fagerholm, Tove Grönroos, Tiina Lipponen, Outi Perhola, Jouko Vepsäläinen, Olof Solin

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

10 Citations (Scopus)

Abstract

INTRODUCTION: The dopamine transporter (DAT) ligand N-(3-fluoropropyl)-2 beta-carbomethoxy-3beta-(4-fluorophenyl)nortropane (beta-CFT-FP) was labeled with fluorine-18, and its biodistribution was evaluated in rats ex vivo.

METHODS: The distribution of 18F radioactivity in the brain and peripheral organs and tissues was determined at several time points 5-120 min after intravenous injection of [18F]beta-CFT-FP.

RESULTS: The highest brain uptake of [18F]beta-CFT-FP was localized in the striatum; limbic structures also exhibited high uptake. Low uptake was found in the cerebellum. The highest ratio of striatum-to-cerebellum uptake, already reached within 5 min, was 3.1. Pretreatment with the selective DAT inhibitor GBR12909 significantly decreased [18F]beta-CFT-FP uptake in the striatum. In most peripheral tissues, the highest uptake was found at 5 min, indicating fast washout of the radioligand. Some accumulation of (18)F radioactivity was seen in bone as a function of time, reflecting defluorination of the radioligand.

CONCLUSION: The results indicate that [18F]beta-CFT-FP is a potential radioligand for studying DAT in vivo with positron emission tomography.

Original language	English
Pages (from-to)	177-83
Number of pages	7
Journal	Nuclear Medicine and Biology
Volume	35
Issue number	2
DOIs	https://doi.org/10.1016/j.nucmedbio.2007.09.006
Publication status	Published - Feb 2008
MoE publication type	A1 Journal article-refereed

Keywords

Animals
Binding, Competitive
Bone and Bones/diagnostic imaging
Cerebellum/diagnostic imaging
Cocaine/analogs & derivatives
Corpus Striatum/diagnostic imaging
Dopamine Plasma Membrane Transport Proteins/antagonists & inhibitors
Dopamine Uptake Inhibitors/pharmacology
Fluorine Radioisotopes/pharmacokinetics
Limbic System/diagnostic imaging
Male
Nortropanes/pharmacokinetics
Piperazines/pharmacology
Radioligand Assay/methods
Radionuclide Imaging
Radiopharmaceuticals/pharmacokinetics
Rats
Rats, Sprague-Dawley
Tissue Distribution

Access to Document

10.1016/j.nucmedbio.2007.09.006

Cite this

@article{7e74fe62142f4f52afeae989969fbbae,

title = "Ex vivo evaluation of N-(3-[18F]fluoropropyl)-2 beta-carbomethoxy-3 beta-(4-fluorophenyl)nortropane in rats",

abstract = "INTRODUCTION: The dopamine transporter (DAT) ligand N-(3-fluoropropyl)-2 beta-carbomethoxy-3beta-(4-fluorophenyl)nortropane (beta-CFT-FP) was labeled with fluorine-18, and its biodistribution was evaluated in rats ex vivo.METHODS: The distribution of 18F radioactivity in the brain and peripheral organs and tissues was determined at several time points 5-120 min after intravenous injection of [18F]beta-CFT-FP.RESULTS: The highest brain uptake of [18F]beta-CFT-FP was localized in the striatum; limbic structures also exhibited high uptake. Low uptake was found in the cerebellum. The highest ratio of striatum-to-cerebellum uptake, already reached within 5 min, was 3.1. Pretreatment with the selective DAT inhibitor GBR12909 significantly decreased [18F]beta-CFT-FP uptake in the striatum. In most peripheral tissues, the highest uptake was found at 5 min, indicating fast washout of the radioligand. Some accumulation of (18)F radioactivity was seen in bone as a function of time, reflecting defluorination of the radioligand.CONCLUSION: The results indicate that [18F]beta-CFT-FP is a potential radioligand for studying DAT in vivo with positron emission tomography.",

keywords = "Animals, Binding, Competitive, Bone and Bones/diagnostic imaging, Cerebellum/diagnostic imaging, Cocaine/analogs & derivatives, Corpus Striatum/diagnostic imaging, Dopamine Plasma Membrane Transport Proteins/antagonists & inhibitors, Dopamine Uptake Inhibitors/pharmacology, Fluorine Radioisotopes/pharmacokinetics, Limbic System/diagnostic imaging, Male, Nortropanes/pharmacokinetics, Piperazines/pharmacology, Radioligand Assay/methods, Radionuclide Imaging, Radiopharmaceuticals/pharmacokinetics, Rats, Rats, Sprague-Dawley, Tissue Distribution",

author = "Teija Koivula and P{\"a}ivi Marjam{\"a}ki and Merja Haaparanta and Veronica Fagerholm and Tove Gr{\"o}nroos and Tiina Lipponen and Outi Perhola and Jouko Veps{\"a}l{\"a}inen and Olof Solin",

year = "2008",

month = feb,

doi = "10.1016/j.nucmedbio.2007.09.006",

language = "English",

volume = "35",

pages = "177--83",

journal = "Nuclear Medicine and Biology",

issn = "0969-8051",

publisher = "Elsevier",

number = "2",

}

TY - JOUR

T1 - Ex vivo evaluation of N-(3-[18F]fluoropropyl)-2 beta-carbomethoxy-3 beta-(4-fluorophenyl)nortropane in rats

AU - Koivula, Teija

AU - Marjamäki, Päivi

AU - Haaparanta, Merja

AU - Fagerholm, Veronica

AU - Grönroos, Tove

AU - Lipponen, Tiina

AU - Perhola, Outi

AU - Vepsäläinen, Jouko

AU - Solin, Olof

PY - 2008/2

Y1 - 2008/2

N2 - INTRODUCTION: The dopamine transporter (DAT) ligand N-(3-fluoropropyl)-2 beta-carbomethoxy-3beta-(4-fluorophenyl)nortropane (beta-CFT-FP) was labeled with fluorine-18, and its biodistribution was evaluated in rats ex vivo.METHODS: The distribution of 18F radioactivity in the brain and peripheral organs and tissues was determined at several time points 5-120 min after intravenous injection of [18F]beta-CFT-FP.RESULTS: The highest brain uptake of [18F]beta-CFT-FP was localized in the striatum; limbic structures also exhibited high uptake. Low uptake was found in the cerebellum. The highest ratio of striatum-to-cerebellum uptake, already reached within 5 min, was 3.1. Pretreatment with the selective DAT inhibitor GBR12909 significantly decreased [18F]beta-CFT-FP uptake in the striatum. In most peripheral tissues, the highest uptake was found at 5 min, indicating fast washout of the radioligand. Some accumulation of (18)F radioactivity was seen in bone as a function of time, reflecting defluorination of the radioligand.CONCLUSION: The results indicate that [18F]beta-CFT-FP is a potential radioligand for studying DAT in vivo with positron emission tomography.

AB - INTRODUCTION: The dopamine transporter (DAT) ligand N-(3-fluoropropyl)-2 beta-carbomethoxy-3beta-(4-fluorophenyl)nortropane (beta-CFT-FP) was labeled with fluorine-18, and its biodistribution was evaluated in rats ex vivo.METHODS: The distribution of 18F radioactivity in the brain and peripheral organs and tissues was determined at several time points 5-120 min after intravenous injection of [18F]beta-CFT-FP.RESULTS: The highest brain uptake of [18F]beta-CFT-FP was localized in the striatum; limbic structures also exhibited high uptake. Low uptake was found in the cerebellum. The highest ratio of striatum-to-cerebellum uptake, already reached within 5 min, was 3.1. Pretreatment with the selective DAT inhibitor GBR12909 significantly decreased [18F]beta-CFT-FP uptake in the striatum. In most peripheral tissues, the highest uptake was found at 5 min, indicating fast washout of the radioligand. Some accumulation of (18)F radioactivity was seen in bone as a function of time, reflecting defluorination of the radioligand.CONCLUSION: The results indicate that [18F]beta-CFT-FP is a potential radioligand for studying DAT in vivo with positron emission tomography.

KW - Animals

KW - Binding, Competitive

KW - Bone and Bones/diagnostic imaging

KW - Cerebellum/diagnostic imaging

KW - Cocaine/analogs & derivatives

KW - Corpus Striatum/diagnostic imaging

KW - Dopamine Plasma Membrane Transport Proteins/antagonists & inhibitors

KW - Dopamine Uptake Inhibitors/pharmacology

KW - Fluorine Radioisotopes/pharmacokinetics

KW - Limbic System/diagnostic imaging

KW - Male

KW - Nortropanes/pharmacokinetics

KW - Piperazines/pharmacology

KW - Radioligand Assay/methods

KW - Radionuclide Imaging

KW - Radiopharmaceuticals/pharmacokinetics

KW - Rats

KW - Rats, Sprague-Dawley

KW - Tissue Distribution

U2 - 10.1016/j.nucmedbio.2007.09.006

DO - 10.1016/j.nucmedbio.2007.09.006

M3 - Article

C2 - 18312827

SN - 0969-8051

VL - 35

SP - 177

EP - 183

JO - Nuclear Medicine and Biology

JF - Nuclear Medicine and Biology

IS - 2

ER -

Ex vivo evaluation of N-(3-[18F]fluoropropyl)-2 beta-carbomethoxy-3 beta-(4-fluorophenyl)nortropane in rats

Abstract

Keywords

Access to Document

Fingerprint

Cite this