High correlation between in vivo 123Iβ-CIT SPECT-CT imaging and post-mortem immunohistochemical findings in the evaluation of lesions induced by 6-OHDA in ratsReport as inadecuate




High correlation between in vivo 123Iβ-CIT SPECT-CT imaging and post-mortem immunohistochemical findings in the evaluation of lesions induced by 6-OHDA in rats - Download this document for free, or read online. Document in PDF available to download.

EJNMMI Research

, 3:46

First Online: 10 June 2013Received: 20 February 2013Accepted: 20 May 2013DOI: 10.1186-2191-219X-3-46

Cite this article as: Bäck, S., Raki, M., Tuominen, R.K. et al. EJNMMI Res 2013 3: 46. doi:10.1186-2191-219X-3-46

Abstract

Background6-Hydroxydopamine 6-OHDA is widely used in pre-clinical animal studies to induce degeneration of midbrain dopamine neurons to create animal models of Parkinson-s disease. The aim of our study was to evaluate the potential of combined single-photon emission computed tomography-computed tomography SPECT-CT for the detection of differences in 6-OHDA-induced partial lesions in a dose- and time-dependent manner using the dopamine transporter DAT ligand 2β-carbomethoxy-3β-4-Iiodophenyltropane Iβ-CIT.

MethodsRats were unilaterally lesioned with intrastriatal injections of 8 or 2 × 10 μg 6-OHDA. At 2 or 4 weeks post-lesion, 40 to 50 MBq Iβ-CIT was administered intravenously and rats were imaged with small-animal SPECT-CT under isoflurane anesthesia. The striatum was delineated and mean striatal activity in the lesioned side was compared to the intact side. After the Iβ-CIT SPECT-CT scan, the rats were tested for amphetamine-induced rotation asymmetry, and their brains were immunohistochemically stained for DAT and tyrosine hydroxylase TH. The fiber density of DAT- and TH-stained striata was estimated, and TH-immunoreactive cells in the rat substantia nigra pars compacta SNpc were stereologically counted.

ResultsThe striatal uptake of Iβ-CIT differed significantly between the lesion groups and the results were highly correlated to both striatal DAT- and TH-immunoreactive fiber densities and to TH-immunoreactive cell numbers in the rat SNpc. No clear progression of the lesion could be seen.

ConclusionsIβ-CIT SPECT-CT is a valuable tool in predicting the condition of the rat midbrain dopaminergic pathway in the unilateral partial 6-OHDA lesion model of Parkinson-s disease and it offers many advantages, allowing repeated non-invasive analysis of living animals.

Keywords6-OHDA β-CIT Rat SPECT AbbreviationsCFT2-β-carbomethoxy-3β-4-fluorophenyltropane

CTComputed tomography

DATDopamine transporter

123Iβ-CIT2β-carbomethoxy-3β-4-Iiodophenyltropane

123IFP-CITN-ω-fluoropropyl-2β-carbomethoxy-3β-4-Iiodophenyltropane

i.pIntraperitoneal

l-DOPAl-3,4-dihydroxyphenylalanine

MFBMedial forebrain bundle

PDParkinson-s disease

PETPositron emission tomography

SERTSerotonin transporter

SNpcSubstantia nigra pars compacta

SPECTSingle-photon emission computed tomography

THTyrosine hydroxylase

6-OHDA6-hydroxydopamine

Electronic supplementary materialThe online version of this article doi:10.1186-2191-219X-3-46 contains supplementary material, which is available to authorized users.

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Author: Susanne Bäck - Mari Raki - Raimo K Tuominen - Atso Raasmaja - Kim Bergström - Pekka T Männistö

Source: https://link.springer.com/







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