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Open Access 01-12-2011 | Original research

Use of [¹⁸F]FDOPA-PET for in vivo evaluation of dopaminergic dysfunction in unilaterally 6-OHDA-lesioned rats

Authors: Kiyoshi Kyono, Tadayuki Takashima, Yumiko Katayama, Toshiyuki Kawasaki, Riyo Zochi, Maki Gouda, Yasuhiro Kuwahara, Kazuhiro Takahashi, Yasuhiro Wada, Hirotaka Onoe, Yasuyoshi Watanabe

Published in: EJNMMI Research | Issue 1/2011

Abstract

Background

We evaluated the utility of L-3,4-dihydroxy-6-[¹⁸F]fluoro-phenylalanine ([¹⁸F]FDOPA) positron emission tomography (PET) as a method for assessing the severity of dopaminergic dysfunction in unilaterally 6-hydroxydopamine (6-OHDA)-lesioned rats by comparing it with quantitative biochemical, immunohistochemical, and behavioral measurements.

Methods

Different doses of 6-OHDA (0, 7, 14, and 28 μg) were unilaterally injected into the right striatum of male Sprague-Dawley rats. Dopaminergic functional activity in the striatum was assessed by [¹⁸F]FDOPA-PET, measurement of striatal dopamine (DA) and DA metabolite levels, tyrosine hydroxylase (TH) immunostaining, and methamphetamine-induced rotational testing.

Results

Accumulation of [¹⁸F]FDOPA in the bilateral striatum was observed in rats pretreated with both aromatic L-amino acid decarboxylase and catechol-O-methyltransferase (COMT) inhibitors. Unilateral intrastriatal injection of 6-OHDA produced a significant site-specific reduction in [¹⁸F]FDOPA accumulation. The topological distribution pattern of [¹⁸F]FDOPA accumulation in the ipsilateral striatum agreed well with the pattern in TH-stained corresponding sections. A significant positive relationship was found between Patlak plot K _i values and striatal levels of DA and its metabolites (r = 0.958). A significant negative correlation was found between both K _i values (r = -0.639) and levels of DA and its metabolites (r = -0.719) and the number of methamphetamine-induced rotations.

Conclusions

K _i values determined using [¹⁸F]FDOPA-PET correlated significantly with the severity of dopaminergic dysfunction. [¹⁸F]FDOPA-PET makes it possible to perform longitudinal evaluation of dopaminergic function in 6-OHDA-lesioned rats, which is useful in the development of new drugs and therapies for Parkinson's disease (PD).

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Title: Use of [18F]FDOPA-PET for in vivo evaluation of dopaminergic dysfunction in unilaterally 6-OHDA-lesioned rats
Authors: Kiyoshi Kyono
Tadayuki Takashima
Yumiko Katayama
Toshiyuki Kawasaki
Riyo Zochi
Maki Gouda
Yasuhiro Kuwahara
Kazuhiro Takahashi
Yasuhiro Wada
Hirotaka Onoe
Yasuyoshi Watanabe
Publication date: 01-12-2011
Publisher: Springer Berlin Heidelberg
Published in: EJNMMI Research / Issue 1/2011
Electronic ISSN: 2191-219X
DOI: https://doi.org/10.1186/2191-219X-1-25

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Use of [¹⁸F]FDOPA-PET for in vivo evaluation of dopaminergic dysfunction in unilaterally 6-OHDA-lesioned rats

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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