Objective: This study evaluated the relationship between the neurodegeneration of the substantia nigra neurons, assessed using Neuromelanin-sensitive MRI, and of the loss of striatal dopaminergic terminals, using [¹¹C]PE2I PET imaging, in individuals with Parkinson’s disease (PD).

Background: A loss of striatal dopaminergic terminals in PD has been noted as has been the loss of neuromelanin (NM) containing neurons in the substantia nigra (SN) evaluated postmortem. Very few studies have investigated in vivo the relationship between the neurodegeneration of the substantia nigra neurons and of the loss of striatal dopaminergic terminals.

Method: A total of 16 individuals with early-stage treatment-naïve PD and 12 age-matched healthy controls (HCs) underwent a [¹¹C]PE2I PET imaging scan assessing dopamine transporter (DAT) expression and 3-Tesla MRI scan quantifying substantia nigra loss by using NM-sensitive MRI. [¹¹C]PE2I non-displaceable binding potential (BP_ND) was estimated using a basis function implementation of the simplified reference tissue model, with the cerebellum as the reference tissue. Substantia nigra loss was measured as reduction in volumes of NM.

Results: We found a reduction of [¹¹C]PE2I BP_ND in the SN, caudate, and putamen (p<0.0001), and a of NM volume in the SN (p<0.0001) in individuals with PD compared to HCs. Lower NM in the SN was correlated with lower [¹¹C]PE2I BP_ND in the SN (p<0.0001), caudate (P<0.0001), and putamen (p<0.0001). Higher MDS-UPDRS-III motor scores correlated with lower NM in the SN (p<0.0001) and with lower [¹¹C]PE2I BP_ND in the caudate (p=0.035), putamen (p=0.0001), and SN (p=0.018).

Conclusion: These findings suggest that this multimodal imaging protocol can provide insight into the relationship between dopaminergic terminals in the striatum and pigmented neurons in the substantia nigra in early PD, and may be useful for assessing the effects of neuroprotective/neurorestorative treatments.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/an-in-vivo-study-of-the-integrity-of-the-nigrostriatal-pathways-in-drug-naive-parkinsons-disease-patients-using-11cpe2i-pet-and-neuromelanin-magnetic-resonance-imaging/