Comparison of 2beta-carbomethoxy-3beta-(4-[18F]fluorophenyl)tropane and N-(3-[18F]fluoropropyl)-2beta-carbomethoxy-3beta-(4-fluorophenyl)nortropane, tracers for imaging dopamine transporter in rat

Päivi Marjamäki; Merja Haaparanta; Sarita Forsback; Veronica Fagerholm; Olli Eskola; Tove Grönroos; Teija Koivula; Olof Solin

doi:10.1007/s11307-009-0278-0

Comparison of 2beta-carbomethoxy-3beta-(4-[18F]fluorophenyl)tropane and N-(3-[18F]fluoropropyl)-2beta-carbomethoxy-3beta-(4-fluorophenyl)nortropane, tracers for imaging dopamine transporter in rat

Päivi Marjamäki, Merja Haaparanta, Sarita Forsback, Veronica Fagerholm, Olli Eskola, Tove Grönroos, Teija Koivula, Olof Solin

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

5 Citations (Scopus)

Abstract

PURPOSE: This study compares 2beta-carbomethoxy-3beta-(4-[(18)F]fluorophenyl)tropane ([(18)F]beta-CFT) and N-(3-[(18)F]fluoropropyl)-2beta-carbomethoxy-3beta-(4-fluorophenyl)nortropane ([(18)F]beta-CFT-FP) as radiotracers for imaging the dopamine transporter (DAT) in rat.

PROCEDURES: Biodistribution, specificity and selectivity of the radiotracers were studied ex vivo in rats pre-treated with specific antagonists for DAT, serotonin transporter (SERT) and noradrenalin transporter (NET) and in control rats. Positron emission tomography (PET) studies were performed using an HRRT scanner. Radiolabelled metabolites were analyzed with thin-layer chromatography.

RESULTS: [(18)F]beta-CFT showed slow kinetics with a maximum striatum/cerebellum uptake ratio of 9.2 at 120 min. [(18)F]beta-CFT-FP showed fast kinetics with a maximum ratio of 3.1 at 5 min. Both tracers bound to DAT. [(18)F]beta-CFT also bound to NET. [(18)F]beta-CFT was more resistant to metabolism than [(18)F]beta-CFT-FP.

CONCLUSIONS: Structural modifications of [(18)F]beta-CFT significantly changed its biological properties, as shown by [(18)F]beta-CFT-FP. [(18)F]beta-CFT is a suitable tracer for both preclinical and human PET studies, but [(18)F]beta-CFT-FP is less suitable as a PET tracer.

Original language	English
Pages (from-to)	269-77
Number of pages	9
Journal	Molecular Imaging and Biology
Volume	12
Issue number	3
DOIs	https://doi.org/10.1007/s11307-009-0278-0
Publication status	Published - Jun 2010
MoE publication type	A1 Journal article-refereed

Keywords

Animals
Brain/metabolism
Dopamine Plasma Membrane Transport Proteins/metabolism
Female
Humans
Male
Metabolome
Nortropanes/chemistry
Positron-Emission Tomography/methods
Radioactive Tracers
Rats
Rats, Sprague-Dawley
Time Factors
Tissue Distribution
Tropanes/chemistry

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10.1007/s11307-009-0278-0

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Marjamäki, P., Haaparanta, M., Forsback, S., Fagerholm, V., Eskola, O., Grönroos, T., Koivula, T., & Solin, O. (2010). Comparison of 2beta-carbomethoxy-3beta-(4-[18F]fluorophenyl)tropane and N-(3-[18F]fluoropropyl)-2beta-carbomethoxy-3beta-(4-fluorophenyl)nortropane, tracers for imaging dopamine transporter in rat. Molecular Imaging and Biology, 12(3), 269-77. https://doi.org/10.1007/s11307-009-0278-0

@article{c41436e3ec8d4b04a5e09a4cad3c2f8f,

title = "Comparison of 2beta-carbomethoxy-3beta-(4-[18F]fluorophenyl)tropane and N-(3-[18F]fluoropropyl)-2beta-carbomethoxy-3beta-(4-fluorophenyl)nortropane, tracers for imaging dopamine transporter in rat",

abstract = "PURPOSE: This study compares 2beta-carbomethoxy-3beta-(4-[(18)F]fluorophenyl)tropane ([(18)F]beta-CFT) and N-(3-[(18)F]fluoropropyl)-2beta-carbomethoxy-3beta-(4-fluorophenyl)nortropane ([(18)F]beta-CFT-FP) as radiotracers for imaging the dopamine transporter (DAT) in rat.PROCEDURES: Biodistribution, specificity and selectivity of the radiotracers were studied ex vivo in rats pre-treated with specific antagonists for DAT, serotonin transporter (SERT) and noradrenalin transporter (NET) and in control rats. Positron emission tomography (PET) studies were performed using an HRRT scanner. Radiolabelled metabolites were analyzed with thin-layer chromatography.RESULTS: [(18)F]beta-CFT showed slow kinetics with a maximum striatum/cerebellum uptake ratio of 9.2 at 120 min. [(18)F]beta-CFT-FP showed fast kinetics with a maximum ratio of 3.1 at 5 min. Both tracers bound to DAT. [(18)F]beta-CFT also bound to NET. [(18)F]beta-CFT was more resistant to metabolism than [(18)F]beta-CFT-FP.CONCLUSIONS: Structural modifications of [(18)F]beta-CFT significantly changed its biological properties, as shown by [(18)F]beta-CFT-FP. [(18)F]beta-CFT is a suitable tracer for both preclinical and human PET studies, but [(18)F]beta-CFT-FP is less suitable as a PET tracer.",

keywords = "Animals, Brain/metabolism, Dopamine Plasma Membrane Transport Proteins/metabolism, Female, Humans, Male, Metabolome, Nortropanes/chemistry, Positron-Emission Tomography/methods, Radioactive Tracers, Rats, Rats, Sprague-Dawley, Time Factors, Tissue Distribution, Tropanes/chemistry",

author = "P{\"a}ivi Marjam{\"a}ki and Merja Haaparanta and Sarita Forsback and Veronica Fagerholm and Olli Eskola and Tove Gr{\"o}nroos and Teija Koivula and Olof Solin",

year = "2010",

month = jun,

doi = "10.1007/s11307-009-0278-0",

language = "English",

volume = "12",

pages = "269--77",

journal = "Molecular Imaging and Biology",

issn = "1860-2002",

publisher = "Springer",

number = "3",

}

Marjamäki, P, Haaparanta, M, Forsback, S, Fagerholm, V, Eskola, O, Grönroos, T, Koivula, T & Solin, O 2010, 'Comparison of 2beta-carbomethoxy-3beta-(4-[18F]fluorophenyl)tropane and N-(3-[18F]fluoropropyl)-2beta-carbomethoxy-3beta-(4-fluorophenyl)nortropane, tracers for imaging dopamine transporter in rat', Molecular Imaging and Biology, vol. 12, no. 3, pp. 269-77. https://doi.org/10.1007/s11307-009-0278-0

Comparison of 2beta-carbomethoxy-3beta-(4-[18F]fluorophenyl)tropane and N-(3-[18F]fluoropropyl)-2beta-carbomethoxy-3beta-(4-fluorophenyl)nortropane, tracers for imaging dopamine transporter in rat. / Marjamäki, Päivi; Haaparanta, Merja; Forsback, Sarita et al.
In: Molecular Imaging and Biology, Vol. 12, No. 3, 06.2010, p. 269-77.

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

TY - JOUR

T1 - Comparison of 2beta-carbomethoxy-3beta-(4-[18F]fluorophenyl)tropane and N-(3-[18F]fluoropropyl)-2beta-carbomethoxy-3beta-(4-fluorophenyl)nortropane, tracers for imaging dopamine transporter in rat

AU - Marjamäki, Päivi

AU - Haaparanta, Merja

AU - Forsback, Sarita

AU - Fagerholm, Veronica

AU - Eskola, Olli

AU - Grönroos, Tove

AU - Koivula, Teija

AU - Solin, Olof

PY - 2010/6

Y1 - 2010/6

N2 - PURPOSE: This study compares 2beta-carbomethoxy-3beta-(4-[(18)F]fluorophenyl)tropane ([(18)F]beta-CFT) and N-(3-[(18)F]fluoropropyl)-2beta-carbomethoxy-3beta-(4-fluorophenyl)nortropane ([(18)F]beta-CFT-FP) as radiotracers for imaging the dopamine transporter (DAT) in rat.PROCEDURES: Biodistribution, specificity and selectivity of the radiotracers were studied ex vivo in rats pre-treated with specific antagonists for DAT, serotonin transporter (SERT) and noradrenalin transporter (NET) and in control rats. Positron emission tomography (PET) studies were performed using an HRRT scanner. Radiolabelled metabolites were analyzed with thin-layer chromatography.RESULTS: [(18)F]beta-CFT showed slow kinetics with a maximum striatum/cerebellum uptake ratio of 9.2 at 120 min. [(18)F]beta-CFT-FP showed fast kinetics with a maximum ratio of 3.1 at 5 min. Both tracers bound to DAT. [(18)F]beta-CFT also bound to NET. [(18)F]beta-CFT was more resistant to metabolism than [(18)F]beta-CFT-FP.CONCLUSIONS: Structural modifications of [(18)F]beta-CFT significantly changed its biological properties, as shown by [(18)F]beta-CFT-FP. [(18)F]beta-CFT is a suitable tracer for both preclinical and human PET studies, but [(18)F]beta-CFT-FP is less suitable as a PET tracer.

AB - PURPOSE: This study compares 2beta-carbomethoxy-3beta-(4-[(18)F]fluorophenyl)tropane ([(18)F]beta-CFT) and N-(3-[(18)F]fluoropropyl)-2beta-carbomethoxy-3beta-(4-fluorophenyl)nortropane ([(18)F]beta-CFT-FP) as radiotracers for imaging the dopamine transporter (DAT) in rat.PROCEDURES: Biodistribution, specificity and selectivity of the radiotracers were studied ex vivo in rats pre-treated with specific antagonists for DAT, serotonin transporter (SERT) and noradrenalin transporter (NET) and in control rats. Positron emission tomography (PET) studies were performed using an HRRT scanner. Radiolabelled metabolites were analyzed with thin-layer chromatography.RESULTS: [(18)F]beta-CFT showed slow kinetics with a maximum striatum/cerebellum uptake ratio of 9.2 at 120 min. [(18)F]beta-CFT-FP showed fast kinetics with a maximum ratio of 3.1 at 5 min. Both tracers bound to DAT. [(18)F]beta-CFT also bound to NET. [(18)F]beta-CFT was more resistant to metabolism than [(18)F]beta-CFT-FP.CONCLUSIONS: Structural modifications of [(18)F]beta-CFT significantly changed its biological properties, as shown by [(18)F]beta-CFT-FP. [(18)F]beta-CFT is a suitable tracer for both preclinical and human PET studies, but [(18)F]beta-CFT-FP is less suitable as a PET tracer.

KW - Animals

KW - Brain/metabolism

KW - Dopamine Plasma Membrane Transport Proteins/metabolism

KW - Female

KW - Humans

KW - Male

KW - Metabolome

KW - Nortropanes/chemistry

KW - Positron-Emission Tomography/methods

KW - Radioactive Tracers

KW - Rats

KW - Rats, Sprague-Dawley

KW - Time Factors

KW - Tissue Distribution

KW - Tropanes/chemistry

U2 - 10.1007/s11307-009-0278-0

DO - 10.1007/s11307-009-0278-0

M3 - Article

C2 - 19949983

SN - 1860-2002

VL - 12

SP - 269

EP - 277

JO - Molecular Imaging and Biology

JF - Molecular Imaging and Biology

IS - 3

ER -

Comparison of 2beta-carbomethoxy-3beta-(4-[18F]fluorophenyl)tropane and N-(3-[18F]fluoropropyl)-2beta-carbomethoxy-3beta-(4-fluorophenyl)nortropane, tracers for imaging dopamine transporter in rat

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