RESUMEN
Background: Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) are atypical parkinsonisms (APs) that are classified as tauopathies. Patients with these APs may present with similar early clinical manifestations to Parkinson's disease (PD), but they prove unresponsive to anti-parkinsonian medications. Objective: The main objective of this meta-analysis was to compare first- and second-generation tau PET tracer efficacy in patients with the APs to identify potential diagnostic biomarkers. Methods: PubMed and Web of Science were searched between January 1, 1999 and December 31, 2022. We included case-control studies that were published in English and report tau PET tracer binding as mean ± SD in at least one region of interest (ROI). Differences in tau PET binding values were meta-analyzed using random-effects meta-analytic models and subgroup analyses based on ROIs in the statistical programming language R (version 4.2.1). Results: Overall, 29 studies with 665 patients were included in the final review. [18F]PI-2620 outperformed first-generation tracers when comparing PSP-HC (g = -1.68, 95% CI: -2.05 to -1.30) and CBD-HC (g = -1.37, 95% CI: -2.25 to -0.49). When comparing PSP-PD, the first-generation tracer, [18F]AV-1451, presented with higher binding to PSP patients (g = -0.80, 95% CI: -1.24 to -0.35). Conclusions: Our results demonstrate the efficacy of [18F]PI-2620 PET in imaging AP-tau. These findings contribute towards identifying a diagnostic imaging biomarker for patients with APs. The main limitation of this study was the heterogeneity of the results. Future studies should conduct AP-PD comparisons with second-generation tracers to confirm the preliminary results found here.
RESUMEN
Atypical parkinsonisms (APs) are a group of diseases linked to tau pathology. These include progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). In the initial stages, these APs may have similar clinical manifestations to Parkinson's disease (PD) and other parkinsonisms: bradykinesia, postural instability, tremor, and cognitive decline. Because of this, one major hurdle is the accurate early diagnosis of APs. Recent advances in positron emission tomography (PET) radiotracer development have allowed for targeting pathological tau in Alzheimer's disease (AD). Currently, work is still in progress for identifying a first-in-class radiotracer for imaging tau in APs. In this review, we evaluate the literature on in vitro and in vivo testing of current tau PET radiotracers in APs. The tau PET tracers assessed include both first-generation tracers ([18F]AV-1451, [18F]FDDNP, [18F]THK derivatives, and [11C]PBB3) and second-generation tracers ([18F]PM-PBB3, [18F]PI-2620, [18F]RO-948, [18F]JNJ-067, [18F]MK-6240, and [18F]CBD-2115). Concerns regarding off-target binding to cerebral white matter and the basal ganglia are still prominent with first-generation tracers, but this seems to have been mediated in a handful of second-generation tracers, including [18F]PI-2620 and [18F]PM-PBB3. Additionally, these two tracers and [18F]MK-6240 show promising results for imaging PSP- and CBD-tau. Overall, [18F]AV-1451 is the most widely studied tracer but the mixed results regarding its efficacy for use in imaging AP-tau is a cause for concern moving forward. Instead, future work may benefit from focusing on the second-generation radiotracers which seem to have a higher specificity for AP-tau than those originally developed for imaging AD-tau.