High correlation between in vivo [123I]β-CIT SPECT/CT imaging and post-mortem immunohistochemical findings in the evaluation of lesions induced by 6-OHDA in rats

Abstract

Background: 6-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-[123I]iodophenyl)tropane ([123I]β-CIT). Methods: Rats 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 [123I]β-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 [123I]β-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. Results: The striatal uptake of [123I]β-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. Conclusions: [123I]β-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. © 2013 Bäck et al.