Objective: This study was designed to investigate the binding of [¹⁸F]-AV-1451 to neuromelanin in parkinsonisms. Uptake in the substantia nigra of Parkinson’s disease (PD) and progressive supranuclear palsy (PSP) patients was predicted to be decreased compared to healthy controls (HC).

Background: [¹⁸F]-AV-1451 is a positron emission tomography (PET) radiotracer designed to bind pathological tau. A post mortem study using [¹⁸F]-AV-1451 discovered off-target binding properties to neuromelanin in the substantia nigra.¹ A subsequent clinical study reported a 30% decrease in [¹⁸F]-AV-1451 binding in the midbrain of PD patients.²

Methods: A total of 12 patients (6 PD: age 63.7±9.61, 3 female; and 6 PSP: age 72.2±6.77, 4 female) and 10 age-matched HC (age 65.9±9.93, 8 female) were recruited. An anatomical MRI and a 90-minute PET scan, using [¹⁸F]-AV-1451, were acquired from all participants. The standardized uptake value ratio (SUVR) from 30 to 60 minutes and 60 to 90 minutes post-injection was calculated for the substantia nigra, using the cerebellar cortex as a reference region. The substantia nigra was delineated using automated region of interest software. An independent samples ANOVA and Bonferroni post hoc testing were used to test for differences in [¹⁸F]-AV-1451 SUVR between the three groups.

Results: There were no significant differences in age and gender across groups. Substantia nigra SUVR from 30-60 minutes was significantly greater in HC (1.33±0.161) compared to PD (1.07±0.117; p=0.009) and PSP (1.09±0.146; p=0.014). The 60-90 minute time point yielded a significantly elevated HC SUVR (1.57±0.235) compared to PD SUVR (1.211±0.258; p=0.039). The substantia nigra SUVR in the HC group was higher than the PSP group (1.27±0.271), though not to a statistically significant degree.

Conclusions:

[¹⁸F]-AV-1451 may be the first PET radiotracer capable of binding neuromelanin, and more importantly, imaging neurodegeneration of the substantia nigra in parkinsonisms. Further testing must be done in PD and atypical parkinsonian disorders to support this off-target use of [¹⁸F]-AV-1451.

References: 1.        Marquie M, Normandin MD, Vanderburg CR, Costantino IM, Bien EA, Rycyna LG, et al. Validating novel tau positron emission tomography tracer [F-18]-AV-1451 (T807) on postmortem brain tissue. Ann Neurol. 2015;78(5):787–800. 2.        Hansen AK, Knudsen K, Lillethorup TP, Landau AM, Parbo P, Fedorova T, et al. In vivo imaging of neuromelanin in Parkinson’s disease using 18 F-AV-1451 PET. Brain. 2016;aww098. http://www.brain.oxfordjournals.org/lookup/doi/10.1093/brain/aww098

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MDS Abstracts - https://www.mdsabstracts.org/abstract/18f-av-1451-binding-to-neuromelanin-in-the-substantia-nigra-in-pd-and-psp/