Abstract
This study investigated binding of [18F]AV-1451 to neuromelanin in the substantia nigra of patients with Parkinson’s disease (PD) and progressive supranuclear palsy (PSP). [18F]AV-1451 is a positron emission tomography 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. A subsequent clinical study reported a 30% decrease in [18F]AV-1451 binding in the midbrain of PD patients. A total of 12 patients and 10 healthy age-matched controls were recruited. An anatomical MRI and a 90-min PET scan, using [18F]AV-1451, were acquired from all participants. The standardized uptake value ratio (SUVR) from 60 to 90 min post-injection was calculated for the substantia nigra, using the cerebellar cortex as the reference region. The substantia nigra was delineated using automated region of interest software. An independent samples ANOVA and LSD post hoc testing were used to test for differences in [18F]AV-1451 SUVR between groups. Substantia nigra SUVR from 60 to 90 min was significantly greater in HC compared to both PSP and PD groups. Although the PD group had the lowest SUVR, there was no significant difference in substantia nigra uptake between PD and PSP. [18F]AV-1451 may be the first PET radiotracer capable of 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.
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Dr. Lorraine Kalia (University of Toronto) and Dr. Elizabeth Slow (University of Toronto) supported patient recruitment for this study.
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SC: acquisition of data, analysis and interpretation of data, draft manuscript for intellectual content; SSC: analysis and interpretation of data, critical revision of manuscript for intellectual content; YK: acquisition of data, critical revision of manuscript for intellectual content; PR: analysis and interpretation of data, critical revision of manuscript for intellectual content; CG: critical revision of manuscript for intellectual content; JK: critical revision of manuscript for intellectual content; AEL: study concept and design, critical revision of manuscript for intellectual content; SH: study concept and design, critical revision of manuscript for intellectual content, study supervision; APS: study concept and design, critical revision of manuscript for intellectual content, study supervision
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Sarah Coakeley: Reports no disclosures; Sang Soo Cho: Reports no disclosures; Yuko Koshimori: Reports no disclosures; Pablo Rusjan: Reports no disclosures; Christine Ghadery: Reports no disclosures; Jinhee Kim: Reports no disclosures; Anthony E. Lang: Reports no disclosures; Sylvain Houle: Reports no disclosures; Antonio P. Strafella: Reports no disclosures
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Study funded by Canadian Institutes of Health Research (MOP-136778) and Parkinson’s Society Canada Fellowship (2015-741)
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Coakeley, S., Cho, S.S., Koshimori, Y. et al. [18F]AV-1451 binding to neuromelanin in the substantia nigra in PD and PSP. Brain Struct Funct 223, 589–595 (2018). https://doi.org/10.1007/s00429-017-1507-y
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DOI: https://doi.org/10.1007/s00429-017-1507-y
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