2-(1-{6-[(2-[F-18]Fluoroethyl) (Methyl)Amino]-2-naphthyl} Ethylidene) Malononitrile-PET for in Vivo Diagnose of Tauopathy in Unclassified Parkinsonism

Summary

The PET tracer \[F18\]-FDDNP has a specific affinity for lesions containing tau protein. The study consists of two phases: * In the first (cross-sectional) phase it will be assessed the uptake of \[18F\]-FDDNP in 10 cases with progressive supranuclear palsy (PSP, a tauopathy) en 10 with multi-system atrophy (MSA, a non-tauopathy), along with 20 individuals with Unclassifiable Parkinsonism, as previously defined in a European cohort study. * In the second (longitudinal) phase it will be prospectively followed the 20 unclassifiable patients (at 6, 12 and 18 months) by means of validated scales and accepted diagnostic criteria in order to try to correlate their eventual clinical diagnosis with baseline PET findings. On this basis, we endeavour to estimate the ability of this technique to detect in vivo underlying tau pathology in subjects initially unclassifiable on clinical grounds. We hypothesized that: 1. Patients with clinically definite PSP will present an increased uptake in basal ganglia, brainstem and cerebellum. 2. Patients with clinically defined MSA will not present specific uptake. 3. Part of unclassifiable patients with parkinsonism will present a pattern of uptake similar to patients with clinically defined PSP and this part along the clinical follow-up will be meet clinical criteria for diagnose of PSP

Timeline

Start

2013-03

Primary completion

2015-12

Completion

2016-02

Publications

• Background Katzenschlager R, Cardozo A, Avila Cobo MR, Tolosa E, Lees AJ. Unclassifiable parkinsonism in two European tertiary referral centres for movement disorders. Mov Disord. 2003 Oct;18(10):1123-31. doi: 10.1002/mds.10523.
• Background Litvan I, Bhatia KP, Burn DJ, Goetz CG, Lang AE, McKeith I, Quinn N, Sethi KD, Shults C, Wenning GK; Movement Disorders Society Scientific Issues Committee. Movement Disorders Society Scientific Issues Committee report: SIC Task Force appraisal of clinical diagnostic criteria for Parkinsonian disorders. Mov Disord. 2003 May;18(5):467-86. doi: 10.1002/mds.10459.
• Background Gilman S, Wenning GK, Low PA, Brooks DJ, Mathias CJ, Trojanowski JQ, Wood NW, Colosimo C, Durr A, Fowler CJ, Kaufmann H, Klockgether T, Lees A, Poewe W, Quinn N, Revesz T, Robertson D, Sandroni P, Seppi K, Vidailhet M. Second consensus statement on the diagnosis of multiple system atrophy. Neurology. 2008 Aug 26;71(9):670-6. doi: 10.1212/01.wnl.0000324625.00404.15.
• Background Golbe LI, Ohman-Strickland PA. A clinical rating scale for progressive supranuclear palsy. Brain. 2007 Jun;130(Pt 6):1552-65. doi: 10.1093/brain/awm032. Epub 2007 Apr 2.
• Background Wenning GK, Tison F, Seppi K, Sampaio C, Diem A, Yekhlef F, Ghorayeb I, Ory F, Galitzky M, Scaravilli T, Bozi M, Colosimo C, Gilman S, Shults CW, Quinn NP, Rascol O, Poewe W; Multiple System Atrophy Study Group. Development and validation of the Unified Multiple System Atrophy Rating Scale (UMSARS). Mov Disord. 2004 Dec;19(12):1391-402. doi: 10.1002/mds.20255.
• Background Wong KP, Wardak M, Shao W, Dahlbom M, Kepe V, Liu J, Satyamurthy N, Small GW, Barrio JR, Huang SC. Quantitative analysis of [18F]FDDNP PET using subcortical white matter as reference region. Eur J Nucl Med Mol Imaging. 2010 Mar;37(3):575-88. doi: 10.1007/s00259-009-1293-8. Epub 2009 Oct 31.
• Background Buongiorno M, Compta Y, Marti MJ. Amyloid-beta and tau biomarkers in Parkinson's disease-dementia. J Neurol Sci. 2011 Nov 15;310(1-2):25-30. doi: 10.1016/j.jns.2011.06.046. Epub 2011 Jul 20.
• Background Smid LM, Vovko TD, Popovic M, Petric A, Kepe V, Barrio JR, Vidmar G, Bresjanac M. The 2,6-disubstituted naphthalene derivative FDDNP labeling reliably predicts Congo red birefringence of protein deposits in brain sections of selected human neurodegenerative diseases. Brain Pathol. 2006 Apr;16(2):124-30. doi: 10.1111/j.1750-3639.2006.00006.x.

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