Novel Radiotracer May Serve as Valuable Diagnostic Biomarker For Supranuclear Palsy

Matthias Brendel, MD, MHBA

Data from a cross-sectional, multicenter evaluation indicated the value of ¹⁸F-PI-2620 to differentiate suspected patients with progressive supranuclear palsy (PSP) using positron emission tomography (PET), potentially facilitating more reliable diagnosis of PSP.

In the first comprehensive in vivo evaluation of a tau-PET tracer, postmortem autoradiography showed blockable ¹⁸F-PI-2620 binding in patients with PSP and no binding in healthy controls.

In an attempt to investigate the potential of the novel tau radiotracer ¹⁸F-PI-2620 as a biomarker in patients with clinically diagnosed PSP, the researchers recruited 60 patients with PSP, 40 (66.7%) of which had Richardson syndrome (RS; 22 men [55.0%]; mean age, 71 [standard deviation (SD), 6] years; mean PSP rating scale score, 38 [SD, 15]; score range, 13-71) and 20 (33.3%) who had PSP without RS (11 men [55.0%]; mean age, 71 [SD, 9] years; mean PSP rating scale score, 24 [SD, 11]; score range, 11-41).

Lead author Matthias Brendel, MD, MHBA, department of nuclear medicine, University of Munich, and colleagues then collected 10 healthy controls with disease (2 men; mean age, 67 [SD, 7] years) and 20 controls with disease—10 (50.0%) with Parkinson disease [PD] and multiple system atrophy (MSA; 7 men; mean age, 61 [SD, 8] years) and 10 (50.0%) with Alzheimer disease (AD; 5 men; mean age, 69 [SD, 10] years).

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The in vivo findings indicated significant elevation of tracer binding in PSP target regions with the strongest differences in PSP versus control groups in the globus pallidus internus (mean distribution volume ratios: PSP-RS, 1.21 [SD, 0.10]; PSP-non-RS, 1.12 [SD, 0.11]; healthy controls, 1.00 [SD, 0.08]; PD/MSA, 1.03 [SD, 0.05]; AD, 1.08 [SD, 0.06]).

Patients with PSP-RS also reported higher binding in the putamen, the substantia nigra, and the dentate nucleus compared with healthy controls, whereas patients with PSP-non-RS did not. Additionally, lower binding indications were observed in the dorsolateral prefrontal cortex and the medial prefrontal cortex in patients with PSP-RS and PSP-non-RS against patients with AD but showed no significant binding differences against a-synucleinopathy patients and healthy cohorts.

At the single-patient level, 34 of 40 individuals (85%) with PSP-RS and 12 of 20 individuals (60%) with PSP-non-RS were classified as PET-positive by the semiquantitative approach, yielding a sensitivity of 85% for PSP-RS and 65% for PSP-non-RS.

Researchers observed that 1 of 10 individuals with PD/MSA and 6 of 10 controls with AD were classified as PET-positive in PSP target regions. Ultimately, it led to an overall specificity of 77% in the combined 30 controls by the semiquantitative approach.

Brendel and colleagues concluded that the “multicenter in vivo data indicate great potential to diagnose patients with suspected PSP using 18F-PI-2620 PET. Dichotomous evaluation at the single-patient level yielded high sensitivity and specificity in strong congruence between semiquantitative and visual approaches for the discrimination between patientswith clinically diagnosed PSP and controls.”

Preliminary evidence also showed that the magnitude of ¹⁸F-PI-2620 binding in PSP target regions differs between PSP phenotypes, thus pointing to the potential of assessing regional phenotype variability in PSPS by in vivo PET imaging. The highest ¹⁸F-PI-2620 binding was observed in PSP-RS followed by PSP with predominant parkinsonism, PSP with predominant frontal presentation, and PSP with predominant corticobasal syndrome.

Additional studies focusing on autopsy validation and longitudinal imaging to test if ¹⁸F-PI-2620 also has potential as a PSP progression biomarker are needed.

REFERENCE

Brendel M, Barthel H, Eimeren TV, et al. Assessment of ¹⁸F-PI-2620 as a biomarker in progressive supranuclear palsy. JAMA Neurol. Published online July 7, 2020. doi: 10.1001/jamaneurol.2020.2526