Prospective F-18 FDOPA PET Imaging Study in Human PD

Abstract

Purpose: We present the findings of our final prospective study submitted to the U.S. Food and Drug Administration (FDA) for New Drug Application (NDA) approval for the use of 3,4-dihydroxy-6-[18F]fluoro-l-phenylalanine (F-18 FDOPA) positron emission tomography (PET) imaging for Parkinson's disease (PD). The primary aim was to determine the sensitivity, specificity, and predictive values of F-18 FDOPA PET in parkinsonian patients with respect to clinical standard-of-truth (SOT). Secondary outcomes included the inter-rater reliability, and correlation of quantitative measures for PET with dopaminergic status.

Methods: In 68 parkinsonian subjects, F-18 FDOPA PET scan from 80 to 100 min was acquired following a CT scan. Scan images were presented to one expert in F-18 FDOPA image interpretation and two physicians with prior experience in I-123 FPCIT single-photon emission computed tomography image interpretation. Fifty-six subjects completed the study with a follow-up for SOT determination. Image readers were blind to the clinical/quantitative data; SOT clinician was blind to the image data.

Results: For 47 of the 56 patients, SOT was in agreement with the PET scan results. For nine patients, SOT suggested dopaminergic deficit, whereas the imaging showed normal uptake. The specificity and positive predictive values are 91% and 92%, respectively, suggesting high probability that those who test positive by the PET scan truly have dopaminergic degeneration. The sensitivity was 73%. Inter-rater agreement was 0.6-0.8 between the different readers.

Conclusion: Our prospective study demonstrates high specificity and moderate sensitivity of F-18 FDOPA PET for PD. We received NDA approval in October 2019.

Supplementary information: The online version contains supplementary material available at 10.1007/s13139-022-00748-4.

Keywords: F-18 FDOPA; PET; Parkinsonism; Prospective study.

Fig. 1

F-18 FDOPA staging. Normal: F-18 FDOPA uptake is obviously increased from the background in both caudate and putamen (cashew-like appearance). Stage 1, Mild: F-18 FDOPA uptake is reduced in posterior putamen on one contralateral side but is preserved on both sides in the caudate nuclei. Stage 2, Moderate: F-18 FDOPA uptake is preserved in caudate but reduced in putamen on both ipsilateral and contralateral sides. Stage 3, Severe: F-18 FDOPA uptake is significantly reduced in putamen on both sides and to a much lesser degree in caudate. The images look oversmoothed because of the slice thickness (19.8 mm) resulting from a sum of central 6 slices of 3.3 mm each; matrix size 128 × 128. For reconstruction parameters, see text in Imaging section

Fig. 2

Study flow diagram. Of the 69 subjects enrolled, 68 underwent F-18 FDOPA PET imaging and 56 of these subjects were further evaluated clinically 6–12 months later by a movement disorder specialist blinded to the PET scan (SOT, standard of truth). Imaging revealed loss of dopaminergic neurons in 26 subjects; loss of dopaminergic neurons was not detected in 30 subjects

Fig. 3

SOR values for positive and negative scans