Second-generation tau PET tracer in situ binding assessed with fluorescence imaging
10 affiliations
- 1Sahlgrenska Academy
- 2University of Gothenburg
- 3Department of Neurodegenerative Disease
- 4Queen Square Institute of Neurology, University College London
- 5Centre for Radiopharmaceutical Chemistry
- 6University College London
- 7Department of Chemistry
- 8Wallenberg Centre for Molecular and Translational Medicine
- 9Department of Neuropsychiatry
- 10Sahlgrenska University Hospital
Abstract
Brain positron emission tomography (PET) imaging is a valuable tool which allows visualization of the pathological structures inside the living patients’ brains. While amyloid-β PET tracers have been in use with Alzheimer’s disease patients in clinics, tau PET tracers have still not entered the clinical routine. Second-generation tau PET tracers have been developed with the aim to overcome the limitations of the first-generation tau PET tracers, such as low sensitivity and off-target binding. However, the detailed pathological characterization of these tracers’ binding is still needed for fully understanding their potential as accurate markers of pathogenic tau. Herein, we focused on the second-generation tau PET tracer Genentech Tau Probe 1 ([18F]GTP1) and made use of the fluorescent properties of its non-radioactive unlabeled variant GTP1 for correlative fluorescence microscopy. The results show that GTP1 binds to tau tangles and neuropil threads (NPTs), but not amyloid-β plaques. Importantly, our results indicate that there is a strong correlation between the fluorescent GTP1 signal and the [18F]GTP1 signal detected with autoradiography, which is currently the standard way of studying the tau PET tracer binding in situ. Together, this data shows the robust application of a non-radioactive tau PET tracer in binding studies in post-mortem tissue and sheds new light on the tau binding properties of GTP1.
Related
- Second-Window Indocyanine Green fluorescence imaging differentiates inflammation from necrotic tissue in early burn wounds
- Second-generation ICG fusion fluorescence endoscopy in pituitary neuroendocrine tumor surgery
- The effects of use of medications on striatal dopamine transporter binding assessed by [123I]I-FP-CIT SPECT in patients with Parkinson’s disease from the PPMI cohort
- Decreased Brain-Derived Neurotrophic Factor, Increased FK506 Binding Protein 5 and Female Sex Are Associated with Multiscale-Assessed Depressive Symptoms During Heart Failure Decompensation: A Polish Prospective Cohort Study
- Association of Multimodal Intracoronary Imaging-Derived Plaque Morphology with the Pathophysiological Disease Patterns Assessed by the Quantitative Flow Ratio-Pullback Pressure Gradient
BibTeX
@misc{antic2026secondgeneration,
title = {{Second-generation tau PET tracer in situ binding assessed with fluorescence imaging}},
author = {Aleksandra Antic and Ambra Dreos and Tammaryn Lashley and Stephen Yong Yo-Ap and Kerstin Sander and Michael Schöll and Jörg Hanrieder},
howpublished = {ChemRxiv},
year = {2026},
month = oct,
doi = {10.26434/chemrxiv.15010881/v1},
url = {https://chemrxiv.org/doi/full/10.26434/chemrxiv.15010881/v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Second-generation tau PET tracer in situ binding assessed with fluorescence imaging
AU - Aleksandra Antic
AU - Ambra Dreos
AU - Tammaryn Lashley
AU - Stephen Yong Yo-Ap
AU - Kerstin Sander
AU - Michael Schöll
AU - Jörg Hanrieder
PY - 2026
DA - 2026/10/22
PB - ChemRxiv
DO - 10.26434/chemrxiv.15010881/v1
UR - https://chemrxiv.org/doi/full/10.26434/chemrxiv.15010881/v1
AB - Brain positron emission tomography (PET) imaging is a valuable tool which allows visualization of the pathological structures inside the living patients’ brains. While amyloid-β PET tracers have been in use with Alzheimer’s disease patients in clinics, tau PET tracers have still not entered the clinical routine. Second-generation tau PET tracers have been developed with the aim to overcome the limitations of the first-generation tau PET tracers, such as low sensitivity and off-target binding. However, the detailed pathological characterization of these tracers’ binding is still needed for fully understanding their potential as accurate markers of pathogenic tau. Herein, we focused on the second-generation tau PET tracer Genentech Tau Probe 1 ([18F]GTP1) and made use of the fluorescent properties of its non-radioactive unlabeled variant GTP1 for correlative fluorescence microscopy. The results show that GTP1 binds to tau tangles and neuropil threads (NPTs), but not amyloid-β plaques. Importantly, our results indicate that there is a strong correlation between the fluorescent GTP1 signal and the [18F]GTP1 signal detected with autoradiography, which is currently the standard way of studying the tau PET tracer binding in situ. Together, this data shows the robust application of a non-radioactive tau PET tracer in binding studies in post-mortem tissue and sheds new light on the tau binding properties of GTP1.
ER -