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Quantification of brain cholinergic denervation in dementia with Lewy bodies using PET imaging with [18F]-FEOBV

Molecular Psychiatry volume 24, pages 322–327 (2019)Cite this article

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To the Editor:

[18F]-fluoroethoxybenzovesamicol ([18F]-FEOBV) is a vesamicol analogue selectively binding the vesicular acetylcholine transporter (VAChT), a protein expressed uniquely by cholinergic neurons [1]. Noninvasive and short duration PET imaging acquisition protocols allowing accurate quantification of VAChT are preferred in patients with dementia because of their limited ability to lay still during prolonged imaging sessions. Recently, Aghourian et al. [2] reported in vivo quantification of brain cholinergic denervation in patients with Alzheimer’s disease (AD) using simplified and noninvasive [18F]-FEOBV PET imaging. These authors applied an abbreviated and noninvasive 30-min imaging protocol with white matter as a reference region to estimate regional gray matter VAChT binding. The white matter reference region was chosen based on nonspecific binding patterns of time-activity curves during late uptake (3–3.5 h) scan phases. This approach departs from previously used cerebellar gray matter reference regions [3]. This is appropriate as the cerebellar cortex contains cholinergic nerve terminals resulting in specific VAChT uptake [4]. Furthermore, cholinergic terminal changes may occur in cerebellar cortices in neurodegenerative disorders, potentially further invalidating the use of this reference region [5]. Using the white matter reference region method, Aghourian et al. [2] reported evidence of prominent cortical VAChT losses in AD patients with the greatest reductions observed in the temporal cortex. No significant differences were found in the hippocampus or subcortical regions between AD patients and age-matched normal control subjects. These observations indicate that septal nuclei and the substantia innominata, the proposed origins of the cholinergic projections to the hippocampus and neocortex, respectively, are differentially involved in AD.

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Acknowledgments

The study was supported by NIH grants P01 NS015655, RO1 NS070856, P50 NS091856, and R21 NS088302. We are indebted to the subjects who participated in this study. Robert Koeppe has received grant support from the NIH. Roger Albin has received grant support from the NIH and the Michael J. Fox Foundation. Kirk Frey has received research support from the NIH, GE Healthcare, and AVID Radiopharmaceuticals (Eli Lilly subsidiary). Martijn Muller has received research support from the NIH, Michael J. Fox Foundation, the Department of Veteran Affairs and Axovant Sciences. Nicolaas Bohnen has received research support from the NIH, Michael J. Fox Foundation, the Department of Veteran Affairs and Axovant Sciences. Dr. Nejad-Davarani reports no sources of funding.

Authors contributions

S.N.D. and N.I.B. were responsible for drafting the text and statistical analysis. R.A.K. was responsible for the time-activity activity curve analysis, kinetic analysis and drafting of figures. K.A.F. was responsible for conception and design of the study K.A.F., R.L.A., M.L.T.M.M., and N.I.B. were responsible for acquisition of data.

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Authors and Affiliations

  1. Radiology, University of Michigan, Ann Arbor, MI, 48104, USA

    Siamak Nejad-Davarani, Robert A. Koeppe, Kirk A. Frey, Martijn L.T.M. Müller & Nicolaas I. Bohnen

  2. Neurology, University of Michigan, Ann Arbor, MI, 48104, USA

    Roger L. Albin, Kirk A. Frey & Nicolaas I. Bohnen

  3. Neurology Service and GRECC, Veterans Administration Ann Arbor Healthcare System, Ann Arbor, MI, 48104, USA

    Roger L. Albin & Nicolaas I. Bohnen

  4. Morris K. Udall Center of Excellence for Parkinson’s Disease Research, University of Michigan, Ann Arbor, MI, USA

    Roger L. Albin, Martijn L.T.M. Müller & Nicolaas I. Bohnen

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  1. Siamak Nejad-Davarani
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Correspondence to Nicolaas I. Bohnen.

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Nejad-Davarani, S., Koeppe, R., Albin, R. et al. Quantification of brain cholinergic denervation in dementia with Lewy bodies using PET imaging with [18F]-FEOBV. Mol Psychiatry 24, 322–327 (2019). https://doi.org/10.1038/s41380-018-0130-5

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