Using [18F]FDOPA PET/CT to Monitor the Effectiveness of Fetal Dopaminergic Grafts in Parkinson Disease Patients

Overview

While positron emission tomography/computed tomography (PET/CT) can assist in the diagnosis of Parkinson disease (PD), it can also potentially help monitor treatment options for PD. One such experimental therapeutic option for PD is fetal dopaminergic transplantation trials. A potential goal of such novel therapies is to replace deficient dopaminergic neurons in PD. Researchers at the University of Saskatchewan have been at the frontier of these exciting treatment options. \[18F\]FDOPA PET/CT imaging has been successfully used by some authors to monitor engraftment and assess efficacy of fetal dopaminergic transplant . This study also aims to utilize \[18F\]FDOPA PET/CT imaging to potentially aid in detecting alterations in the dopaminergic pathway from these innovative surgical treatment options. There are two main objectives of this study: 1) Evaluate the effectiveness of fetal dopaminergic grafts in patients with PD using FDOPA PET imaging pre and post-surgical implantation and a secondary longer term goal 2) Correlate the \[18F\]FDOPA PET/CT findings in early PD with post-mortem pathological analyses of PD

Since the progression of PD is in most cases inexorable, there is an urgent need for curative or restorative treatments, especially for patients whose response to pharmaceutical treatment is marred by levodopa-evoked dyskinesias, or intolerable on-off fluctuations. This project focuses on the option of surgical implantation of embryonic dopamine neurons. Despite promising reports in some early case studies, this daring approach has not always shown consistent clinical outcomes. The factors responsible for this state of affairs remain uncertain, although some studies showed significantly better clinical outcome in younger PD patients (≤ 60 years) as compared to older patients (≥ 60 years). In a number of small clinical studies, researchers at the University of Saskactchewan have shown one of the most consistent improvements in clinical outcomes in fetal dopaminergic grafts, as has been confirmed in a recent review of the literature. Follow-up FDOPA-PET studies have linked enhanced tracer uptake in target regions to persistent improvements in unified parkison disease rating scale (UPDRS), and FDOPA-PET is informative about the relationship between targeting of specific striatal regions and the occurrence of dyskinesias. Co-aaplicants of this research study have received approval and funding to undertake a new clinical trial of fetal dopaminergic neurons for the treatment of advanced and otherwise refractory PD. The main objective of the present study is to correlate the clinical outcomes of PD patients who undergo fetal dopamine neuron transplantation in the new study protocol with changes in FDOPA-PET/CT. Neurologists at the University of Saskachewan and the Royal University Hospital-Saskatoon have assembled an extensive database of PD patients which have been followed prospectively for as long as a decade. As noted above, the relationship between FDOPA-PET/CT and post-mortem findings is poorly documented in small patient samples, even though autopsy findings remain the gold standard for differential diagnosis of parkinsonian syndromes, as noted above. The established reputations of these neurologists in the PD community continues to be an important prerequisite for brain banking in Saskatchewan, and an important side objective of this project is to integrate molecular imaging with prospective post mortem analysis of extensively-documented PD patients.