Use of ¹¹C-PE2I PET in Differential Diagnosis of Parkinsonian Disorders

Abstract

In idiopathic Parkinson disease and atypical parkinsonian disorders, central dopaminergic and overall brain functional activity are altered to different degrees, causing difficulties in achieving an unambiguous clinical diagnosis. A dual examination using ¹²³I-FP-CIT (¹²³I-N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane, or ¹²³I-ioflupane) SPECT and¹⁸F-FDG PET provides complementary information on dopamine transporter (DAT) availability and overall brain functional activity, respectively. Parametric images based on a single, dynamic ¹¹C-PE2I (N-(3-iodoprop-2E-enyl)-2β-carbomethoxy-3β-(4-methyl-phenyl)nortropane) scan potentially supply both DAT availability (nondisplaceable binding potential [BP_ND]) and relative cerebral blood flow (relative delivery [R₁]) at voxel level. This study aimed to evaluate the validity of ¹¹C-PE2I PET against the dual-modality approach using ¹²³I-FP-CIT SPECT and ¹⁸F-FDG PET. Methods: Sixteen patients with parkinsonian disorders had a dual examination with ¹⁸F-FDG PET and ¹²³I-FP-CIT SPECT following clinical routines and additionally an experimental ¹¹C-PE2I PET scan. Parametric BP_ND and R₁ images were generated using receptor parametric mapping with the cerebellum as a reference. T1-weighted MR imaging was used for automated definition of volumes of interest (VOI). The DAT VOIs included the basal ganglia, whereas the overall brain functional activity was examined using VOIs across the brain. BP_ND and R₁ values were compared with normalized ¹²³I-FP-CIT and ¹⁸F-FDG uptake values, respectively, using Pearson correlations and regression analyses. In addition, 2 masked interpreters evaluated the images visually, in both the routine and the experimental datasets, for comparison of patient diagnoses. Results: Parametric ¹¹C-PE2I BP_ND and R₁ images showed high consistency with ¹²³I-FP-CIT SPECT and ¹⁸F-FDG PET images. Correlations between ¹¹C-PE2I BP_ND and ¹²³I-FP-CIT uptake ratios were 0.97 and 0.76 in the putamen and caudate nucleus, respectively. Regional ¹¹C-PE2I R₁ values were moderately to highly correlated with normalized ¹⁸F-FDG values (range, 0.61–0.94). Visual assessment of DAT availability showed a high consistency between ¹¹C-PE2I BP_ND and ¹²³I-FP-CIT images, whereas the consistency was somewhat lower for appraisal of overall brain functional activity using ¹²³I-FP-CIT and ¹⁸F-FDG images. Substantial differences were found between clinical diagnosis and both neuroimaging diagnoses. Conclusion: A single, dynamic ¹¹C-PE2I PET investigation is a powerful alternative to a dual examination with ¹²³I-FP-CIT SPECT and ¹⁸F-FDG PET for differential diagnosis of parkinsonian disorders. A large-scale patient study is, however, needed to further investigate distinct pathologic patterns in overall brain functional activity for various parkinsonian disorders.