Prospective FDOPA PET imaging study in human PD :our final step towards NDA approval

1565 Objectives: We present the findings of our final prospective study submitted to FDA for NDA approval for the use of F18 FDOPA PET imaging for PD diagnosis. The primary aim was to determine the sensitivity, specificity, and predictive values of Fluorodopa F 18 PET in parkinsonian patients with respect to clinical standard-of-truth (SOT). Secondary outcomes included the inter-rater reliability of three PET readers; correlation of quantitative measures for PET with dopaminergic status; and patient safety during scanning. Methods: 56 parkinsonian subjects (average age 66y, disease duration 36 months) completed the study within 6-12 month follow-up for SOT determination by movement disorders specialist. Scan images were presented to one neurologist with expertise in FDOPA image interpretation and two nuclear medicine physicians with prior experience in DAT image interpretation. Images were read according to a Yes (Positive)/No (Negative) choice on reduced FDOPA uptake vs normal within a framework of qualitative guidelines that defined characteristics of putamen/caudate uptake. Image readers were blind to the clinical data; SOT clinician was blind to the image data. A 3D PET scan from 80 to 100 minutes was acquired following a CT scan. A single summed image (6 slices, each 3.3 mm) was generated for visual reading. Results: For 47 of the 56 patients, SOT was in agreement with the PET scan results. For 9 patients, SOT suggested dopaminergic deficit, whereas the imaging showed normal uptake. The specificity and PPV are 91% and 92%, respectively suggesting high probability that those who test positive by the PET scan truly have dopaminergic degeneration. The sensitivity and NPV were slightly lower, at 73% and 70%, respectively. Inter-rater agreement was 0.63-0.75 between different readers. No serious adverse events were reported. Quantitative imaging results will be presented elsewhere. Discussion: Our prospective study demonstrates high specificity and sensitivity of Fluorodopa F-18 PET for PD. We received NDA approval in Dec 2019 and are currently pursuing reimbursement for these studies.