Assessment of striatal and extrastriatal [18F]fluoroDOPA uptake by a Silicon Photomultiplier PET camera in Parkinson’s disease

For clinical Parkinson diagnostics, [18F]fluoroDOPA Positron Emission Tomography is restricted to striatal uptake assessment. DOPA is decarboxylated into dopamine by the aromatic ʟ-amino acid decarboxylase (AADC) and stored in presynaptic vesicles. Therefore, it provides an in vivo measurement of AADC activity and presynaptic storage. This can occur outside of the striatum and may apply to other neuroamines. Extrastriatal [18F]fluoroDOPA uptake has been previously studied using brain dedicated PET cameras and long dynamic acquisition protocols. We investigated the ability of new high-resolution Silicon Photomultipliers (SiPM) PET cameras to evaluate these extrastriatal [18F]fluoroDOPA uptake sites and the changes occurring in Parkinson’s disease patients (PD). Besides striatum, [18F]fluoroDOPA uptake was measured in the following structures: periaqueductal gray (PAG), substantia nigra (SN), anterior cingulate (AC) and pineal gland (PG) in 42 essential tremor patients (ET), 50 early Parkinson’s disease patients (PD) and 26 with high grade gliomas (HGG). Visual analysis was performed on ET and PD patients by 3 observers to assess the diagnostic value of the “Mickey mouse sign” related to the abnormal visualisation of PAG and SN uptake. The sensitivity, specificity and accuracy of the sign for the diagnosis of PD were 95%, 100% and 97% respectively. Quantitative analysis showed higher PAG uptake in PD versus ET patients (2.09 ± 0.13 vs. 1.96 ± 0.20; p = 0.0003). No significant difference was found for SN and PG. AC uptake was lower in PD versus ET (1.17 ± 0.14 vs. 1.24 ± 0.17; p = 0.02). Dual phase imaging in HGG patients showed a high increase of uptake between 20 and 90 min after tracer injection for all structures except for AC, suggesting a non-AADC related uptake mechanism in this region. Recent SiPM PET/CT cameras allow measurements of extrastriatal [18F]fluoroDOPA uptake in a clinical setting using short static acquisitions. The “Mickey mouse” sign in PD is related to a decrease of striatal uptake which makes normal SN uptake relatively more visible and to an increase of PAG uptake. The latter is probably related to upregulation AADC in PAG serotoninergic neurons in PD patients and suggests that [18F]fluoroDOPA imaging could be used to monitor these neurons.