Characterization of the binding of tau imaging ligands to melanin-containing cells: putative off-target-binding site

Annals of Nuclear Medicine
Tetsuro TagoKenji Ishii

Abstract

Amyloid-β plaques and neurofibrillary tangles composed of tau protein are the neuropathological hallmarks of Alzheimer's disease. In recent years, marked progress has been made in Alzheimer's disease research using tau ligands for positron emission tomography (PET). However, the issue of off-target binding, that is, the binding of ligands to regions without tau pathology, remains unresolved. Tissues with melanin-containing cells (MCCs) have been suggested as binding targets for tau ligands. In the present study, we characterized the MCC-binding properties of representative tau PET ligands. Autoradiographic studies of [18F]AV-1451 and [18F]THK5351 were conducted using postmortem human midbrain sections. Saturation-binding assays of [18F]AV-1451 and [18F]THK5351 were performed with B16F10 melanoma cells. The blocking effects of 25 compounds against [18F]THK5351 binding to B16F10 cells were used to investigate the relationship between chemical structure and MCC binding. Autoradiography demonstrated specific binding of the radioligands in the substantia nigra. [18F]AV-1451 and [18F]THK5351 exhibited saturable binding to melanoma cells ([18F]AV-1451: Kd = 669 ± 196 nM, Bmax = 622 ± 269 pmol/mg protein; [18F]THK5351: Kd = 441 ± 126 n...Continue Reading

References

Jan 1, 1991·Acta Neuropathologica·H Braak, E Braak
Jun 1, 1974·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·B Y YooA Persson
Jul 4, 2001·Nature Reviews. Neuroscience·M Goedert
Mar 3, 2004·Annals of Neurology·William E KlunkBengt Långström
Mar 23, 2006·Nature Reviews. Neuroscience·Moussa B H YoudimKeith F Tipton
May 24, 2007·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Robert B InnisRichard E Carson
Jul 8, 2009·International Journal of Molecular Sciences·Te-Sheng Chang
Dec 14, 2012·Journal of Alzheimer's Disease : JAD·David T ChienHartmuth C Kolb
Feb 14, 2013·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Junchao TongStephen J Kish
Jul 17, 2013·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Nobuyuki OkamuraYukitsuka Kudo
Nov 13, 2013·Nature Reviews. Neurology·Ezio Giacobini, Gabriel Gold
Nov 7, 2015·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Ryuichi HaradaYukitsuka Kudo
Dec 25, 2015·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Tetsuro TagoYukitsuka Kudo
Jan 12, 2016·Biomolecules·Ryuichi HaradaYukitsuka Kudo
May 18, 2016·Brain : a Journal of Neurology·Allan K HansenPer Borghammer
May 28, 2016·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Eric D HostetlerJeffrey L Evelhoch
Jun 15, 2016·Acta Neuropathologica Communications·Val J LoweMelissa E Murray
Jun 18, 2016·Archives of Toxicology·Oskar Karlsson, Nils Gunnar Lindquist
Apr 1, 2017·Alzheimer's Research & Therapy·Kok Pin NgPedro Rosa-Neto
Jun 2, 2017·Movement Disorders : Official Journal of the Movement Disorder Society·Alexandra Perez-SorianoA Jon Stoessl
Jul 8, 2017·NPJ Parkinson's Disease·Sarah Coakeley, Antonio P Strafella
Sep 3, 2017·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Ryuichi HaradaNobuyuki Okamura
Sep 8, 2017·International Journal of Molecular Sciences·Anne BüngelerOliver I Strube
Dec 17, 2017·Advanced Drug Delivery Reviews·Anna-Kaisa RimpeläEva M Del Amo
Sep 7, 2018·Frontiers in Neuroscience·Ryuichi HaradaKazuhiko Yanai
Nov 7, 2018·Journal of Medicinal Chemistry·Paulina JakubiakRubén Alvarez-Sánchez

❮ Previous
Next ❯

Citations

Dec 19, 2019·European Journal of Nuclear Medicine and Molecular Imaging·Jolien SchaeverbekeRik Vandenberghe
Jan 28, 2021·Seminars in Nuclear Medicine·Aren van WaardeRudi A J O Dierckx
Jan 23, 2022·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Nathalie MertensMichel Koole

❮ Previous
Next ❯

Related Concepts

Related Feeds

Alzheimer's Disease: Neuroimaging

Neuroimaging can help identify pathological hallmarks of Alzheimer's disease (AD). Here is the latest research on neuroimaging modalities, including magnetic resonance imaging and positron emission tomography, in AD.

Alzheimer's Disease: Tau & TDP-43

Alzheimer's disease is a neurodegenerative disease. This feed focuses on the underlying role of tau proteins and TAR DNA-binding protein 43, as well as other genetic factors, in Alzheimer's disease.