Diagnostic value of striatal 18F-FP-DTBZ PET in Parkinson's disease

Abstract

Background: ¹⁸F-FP-DTBZ has been proven as a biomarker for quantifying the concentration of presynaptic vesicular monoamine transporter 2 (VMAT2). However, its clinical application is still limited.

Objectives: To evaluate the difference in dopaminergic integrity between patients with Parkinson's disease (PD) and healthy controls (HC) using ¹⁸F-FP-DTBZ PET in vivo and to determine the diagnostic value of standardized uptake value ratios (SUVRs) using the Receiver Operating Characteristic (ROC) curve.

Methods: A total of 34 PD and 31 HC participants were enrolled in the PET/MR derivation cohort, while 89 PD and 18 HC participants were recruited in the PET/CT validation cohort. The Hoehn-Yahr Scale and the third part of the MDS-Unified Parkinson's Disease Rating Scale (MDSUPDRS-III) were used to evaluate the disease staging and severity. All assessments and PET scanning were performed in drug-off states. The striatum was segmented into five subregions as follows: caudate, anterior dorsal putamen (ADP), anterior ventral putamen (AVP), posterior dorsal putamen (PDP), and posterior ventral putamen (PVP) using automatic pipeline built with the PMOD software (version 4.105). The SUVRs of the targeted subregions were calculated using the bilateral occipital cortex as the reference region.

Results: Regarding the diagnostic value, ROC curve and blind validation showed that the contralateral PDP (SUVR = 3.43) had the best diagnostic accuracy (AUC = 0.973; P < 0.05), with a sensitivity of 97.1% (95% CI: 82.9-99.8%), specificity of 100% (95% CI: 86.3-100%), positive predictive value (PPV) of 100% (95% CI: 87.0-100%), negative predictive value (NPV) of 96.9% (95% CI: 82.0-99.8%), and an accuracy of 98.5% for the diagnosis of PD in the derivation cohort. Blind validation of ¹⁸F-FP-DTBZ PET imaging diagnosis was done using the PET/CT cohort, where participants with a SUVR of the PDP <3.43 were defined as PD. Kappa test showed a consistency of 0.933 (P < 0.05) between clinical diagnosis and imaging diagnosis, with a sensitivity of 98.9% (95% CI: 93.0-99.9%), specificity of 94.4% (95% CI: 70.6-99.7%), PPV of 98.9% (95% CI: 93.0-99.9%), NPV of 94.4% (95% CI: 70.6-99.7%), and a diagnostic accuracy of 98.1%.

Conclusions: Our results showed that an SUVR threshold of 3.43 in the PDP could effectively distinguish patients with PD from HC.

Keywords: 18F-FP-DTBZ; Parkinson’s disease; VMAT2; diagnostic value; positron emission tomography.

FIGURE 1

The ¹⁸F-FP-DTBZ PET image template with striatum regions was superimposed and shown in sagittal (A) and axial (B) positions. The striatum of each side was divided into five subregions as follows: caudate(red), anterior dorsal putamen (ADP, purple), anterior ventral putamen (AVP, dark purple), posterior dorsal putamen (PDP, pale purple), posterior ventral putamen (PVP, blue). The occipital lobe(violet) was used as the reference region.

FIGURE 2

Scatterplots with bars of the diagnostic SUVR of each subdivisions. HC-R, the right side of healthy controls in the validation cohort; HC-L, the left side of healthy controls in the validation cohort; PD-R, the right side of PD patients in the validation cohort; PD-L, the left side of PD patients in the validation cohort; I*-(ipsilateral), brain regions located at the side of clinical symptoms onset (PD group) in the derivation cohort; C*-(contralateral), brain regions located opposite to the side of clinical symptoms onset (PD group) in the derivation cohort; Cau, caudate; ADP, anterior dorsal putamen; AVP, anterior ventral putamen; PDP, posterior dorsal putamen; PVP, posterior ventral putamen. We presented the right and left side of healthy controls and PD patients in the validation cohort, but did not distinguish between the ipsilateral and contralateral sides of the PD patients. Then, the optimal diagnostic SUVRs of each subregion were put into the corresponding subregion of the validation cohort, and those with less than the corresponding diagnostic SUVR were defined as “PD patients.” Scatterplots with bars of each subdivision showed that the diagnostic SUVR of contralateral posterior dorsal putamen had the best diagnostic accuracy of 98.1%. The vertical line represents the cut-off value defined in the PET/MRI cohort.