Simple Ratio Analysis of ¹⁸F-Fluorodopa Uptake in Striatal Subregions Separates Patients with Early Parkinson Disease from Healthy Controls

Abstract

6-18 F-fluoro-L-dopa ( 18 F-FDOPA) is widely used to investigate dopaminergic hypofunction, for instance, in Parkinson disease (PD). Conventionally, a 90-min scan with either a graphical or a metabolite-purified plasma input approach has been used for quantification. In the clinical setting, to increase compliance, especially in patients with more advanced disease, and to increase the efficacy of tracer and scanner time use, a shorter acquisition and a simple quantitative analysis are desirable. Taking into account the asymmetry of clinical symptoms and the uneven distribution of striatal dopaminergic hypofunction may also improve the use of 18 F-FDOPA PET in early disease detection. Therefore, we compared subregional striatal 18 F-FDOPA PET data from a large group of nonmedicated patients with early PD and a set of healthy elderly volunteers to find out whether a simple ratio approach would reliably separate PD patients from healthy controls. Methods: A total of 89 nonmedicated patients with early PD and 21 healthy volunteers were studied with 18 F-FDOPA PET, and both a region-to-reference (striatal-to-occipital) ratio (SOR) calculated from 75 to 90 min after injection and a graphical analysis of data calculated from 15 to 90 min after 18 F-FDOPA injection (yielding the influx constant [K i ref ]) were used. Results: Both SOR and K i ref values in the PD patients were lowest, relative to those in the healthy controls, in the posterior putamen contralateral to the side with predominant clinical symptoms. The contralateral posterior putamen showed the largest areas under the receiver operating characteristic (ROC) curve-0.994 for SOR and 0.998 for K i ref -indicating excellent separation of the PD and control groups. The caudate nucleus and the ventral striatum were less impressive in this respect. Conclusion: A single 15-min scan 75 min after tracer injection seems to be sufficient for separating patients with PD from healthy controls in a clinical research environment. This method represents a powerful and economical alternative for research on the disease mechanism and differential diagnosis.

Subregional Patterns of Preferential Striatal Dopamine Transporter Loss Differ in Parkinson Disease, Progressive Supranuclear Palsy, and Multiple-System Atrophy

“…These results are consistent with previous 123 I-b-CIT studies (17,27). However, the relative sparing of DAT loss in the VP in PD resulted in a ventrodorsal gradient of putaminal DAT loss.…”

“…The striatum was further divided into more substructures-VS, VP, AP, PP, AC, and AP-in the present study than in previous studies (17,25) because of the higher resolution offered by a new-generation PET scanner (26). This scenario enabled us to understand the complex functional anatomy of this structure, which is crucial to understanding the pathophysiology of parkinsonian disorders.…”

“…Because of the improved resolution of PET instrumentation, subdividing the putamen into multiple parts was recently attempted in a VOI-based study (38). In addition, Jokinen et al (17) reported the reliable detection of early PD by ratio analysis of 6-18 F-flouro-L-dopa uptake in striatal subregions. In the present study, however, spatially normalized 18 F-FP-CIT PET images of some patients showed misregistration with predefined VOI templates and were ultimately excluded from the VOI analysis.…”

“…18 F-fluorinated-N-3-fluoropropyl-2-b-carboxymethoxy-3-b-(4-iodophenyl)nortropane ( 18 F-FP-CIT) PET/CT, which has recently become available for DAT imaging in clinical practice, has better spatial resolution and more sophisticated attenuation correction than SPECT (16). Thus, it is possible to use 18 F-FP-CIT PET to evaluate subregional changes in the striatal DAT (17) and to differentiate parkinsonian disorders on the basis of the more asymmetric and pronounced loss of the posterior putamen (PP) in PD than in APD (14,15).…”

Multiagent imaging of the brain

“…Jokinen et al [65] showed a lower striatal-to-occipital ratio in PD patients compared with controls, with the lowest ratio being found in the posterior putamen contralateral to the side of predominant clinical symptoms. However, because of up-regulation of AADC activity in the surviving cells, 18 F-DOPA may underestimate the severity of nigrostriatal loss, especially in the early stages of disease [66].…”