Objective: We investigated whether 18F-DPA714 imaging could be a sensitive marker of neuroinflammation in Parkinson disease (PD). We took into account the polymorphism of TSPO expression in our subjects and previously validated image quantification to measure the regional distribution of activated microglia in PD patients compared to healthy controls (HC). Dopaminergic cell loss was measured using dopamine transporter imaging to correlate neuroinflammation with dopaminergic denervation.

Background: In PD, neuroinflammation might contribute to the progression of dopaminergic degeneration. Positron emission tomography (PET) imaging of glial activation targets the translocator protein 18-kDa (TSPO) up-regulated under inflammatory condition. Some PET studies have investigated neuroinflammation in PD using 11C-PK11195, 11C-DPA713 and 18F-FEPPA radioligands, but provided variable results.

Method: PD patients (n=20, 64.0 ± 9.8 y.o., motor UPDRS range [6-34]) and age-matched HC (n=29, 54.4 ± 15.5 y.o.) were enrolled. The genotyping of the polymorphism in the TSPO gene revealed 13/13 mixed affinity binders (MABs) and 7/13 high affinity binders (HABs)) in patients and HC, respectively. PET data were acquired on a HRRT scanner for 90 minutes and 60 min after injection of 18F-DPA714 and 11C-PE2I. An AAL atlas including 90 lateralized ROIs was applied on individual MRI. A supervised cluster analysis [1] extracted an individual reference region used in a reference Logan analysis yielding to BPND-DPA714 estimates. The SRTM with cerebellum as reference was used to extract BPND-PE2I from 11C-PE2I images.

Results: Factorial ANOVA revealed that BPND-DPA714 in the Substantia nigra contralateral to the clinically most affected side were significantly higher in PD patients than in HC. The signal in the most affected SN was significantly higher than in the less affected side. Significant increase was also observed in both Caudate and thalami. There was no significant correlation between BPND-DPA714 and age, disease progression or striatal BPND-PE2I. In both groups, 18F-DPA714 binding was higher in HABs than in MABS in all ROIs.

Conclusion: 18F-DPA714 reveals neuroinflammation in the most affected Substanita nigra of PD patients and the binding is not correlated with disease severity.

References: [1] Garcia-Lorenzo, D. et al. Validation of an automatic reference region extraction for the quantification of [(18)F]DPA-714 in dynamic brain PET studies. J Cerebr Blood Flow Metab 2018;38: 333-46.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/18f-dpa714-pet-reveals-neuroinflammatory-activity-in-the-substantia-nigra-of-patients-with-parkinson-disease/