Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Molecular Imaging and Biology
Published in: Molecular Imaging and Biology 6/2023

Open Access 14-08-2023 | Alzheimer's Disease | Research Article

A Novel Near-Infrared Fluorescence Probe THK-565 Enables In Vivo Detection of Amyloid Deposits in Alzheimer’s Disease Mouse Model

Authors: Fumito Naganuma, Daiki Murata, Marie Inoue, Yuri Maehori, Ryuichi Harada, Shozo Furumoto, Yukitsuka Kudo, Tadaho Nakamura, Nobuyuki Okamura

Published in: Molecular Imaging and Biology | Issue 6/2023

Login to get access

Abstract

Purpose

Noninvasive imaging of protein aggregates in the brain is critical for the early diagnosis, disease monitoring, and evaluation of the effectiveness of novel therapies for Alzheimer’s disease (AD). Near-infrared fluorescence (NIRF) imaging with specific probes is a promising technique for the in vivo detection of protein deposits without radiation exposure. Comprehensive screening of fluorescent compounds identified a novel compound, THK-565, for the in vivo imaging of amyloid-β (Aβ) deposits in the mouse brain. This study assessed whether THK-565 could detect amyloid-β deposits in vivo in the AD mouse model.

Procedures

The fluorescent properties of THK-565 were evaluated in the presence and absence of Aβ fibrils. APP knock-in (APP-KI) mice were used as an animal model of AD. In vivo NIRF images were acquired after the intravenous administration of THK-565 and THK-265 in mice. The binding selectivity of THK-565 to Aβ was evaluated using brain slices obtained from these mouse models.

Results

The fluorescence intensity of the THK-565 solution substantially increased by mixing with Aβ fibrils. The maximum emission wavelength of the complex of THK-565 and Aβ fibrils was 704 nm, which was within the optical window range. THK-565 selectively bound to amyloid deposits in brain sections of APP-KI mice After the intravenous administration of THK-565, the fluorescence signal in the head of APP-KI mice was significantly higher than that of wild-type mice and higher than that after administration of THK-265. Ex vivo analysis confirmed that the THK-565 signal corresponded to Aβ immunostaining in the brain sections of these mice.

Conclusions

A novel NIRF probe, THK-565, enabled the in vivo detection of Aβ deposits in the brains of the AD mouse model, suggesting that NIRF imaging with THK-565 could non-invasively assess disease-specific pathology in AD.
Literature
1.
Zwan MD, Okamura N, Fodero-Tavoletti MT et al (2014) Voyage au bout de la nuit: Aβ and tau imaging in dementias. Q J Nucl Med Mol Imaging 58:398–412
2.
Okamura N, Harada R (2022) PET imaging of amyloid and tau in Alzheimer’s disease. In Mori N (ed.) Aging Mechanisms II : Longevity, Metabolism, and Brain Aging. Singapore: Springer Nature Singapore, 307–323
3.
Okamura N, Fodero-Tavoletti MT, Kudo Y et al (2009) Advances in molecular imaging for the diagnosis of dementia. Expert Opin Med Diagn 3:705–716CrossRefPubMed
4.
Rai H, Gupta S, Kumar S et al (2022) Near-Infrared Fluorescent Probes as Imaging and Theranostic Modalities for Amyloid-Beta and Tau Aggregates in Alzheimer’s Disease. J Med Chem 65:8550–8595CrossRefPubMed
5.
Hintersteiner M, Enz A, Frey P et al (2005) In vivo detection of amyloid-β deposits by near-infrared imaging using an oxazine-derivative probe. Nat Biotechnol 23:577–583
6.
Chen CP, Liang ZY, Zhou B et al (2018) In Vivo Near-Infrared Two-Photon Imaging of Amyloid Plaques in Deep Brain of Alzheimer’s Disease Mouse Model. ACS Chem Neurosci 9:3128–3136CrossRefPubMed
7.
Nesterov EE, Skoch J, Hyman BT, Klunk WE, Bacskai BJ, Swager TM (2005) In vivo optical imaging of amyloid aggregates in brain: design of fluorescent markers. Angew Chem Int Ed Engl 44:5452–5456CrossRefPubMed
8.
Liu Y, Zhuang D, Wang J et al (2022) Recent advances in small molecular near-infrared fluorescence probes for a targeted diagnosis of the Alzheimer disease. Analyst 147:4701–4723CrossRefPubMed
9.
Quan L, Moreno-Gonzalez I, Xie Z et al (2023) A near-infrared probe for detecting and interposing amyloid beta oligomerization in early Alzheimer’s disease. Alzheimers Dement 19:456–466CrossRefPubMed
10.
Wu J, Shao C, Ye X et al (2021) InVivo brain imaging of amyloid-β aggregates in Alzheimer’s disease with a near-infrared fluorescent probe. ACS Sens 6:863–870
11.
Zeng F, Yang J, Li X et al (2020) Versatile near-infrared fluorescent probe for in vivo detection of Aβ oligomers. Bioorg Med Chem 28:115559
12.
Chen Y, Yuan C, Xie T et al (2020) N, O-Benzamide difluoroboron complexes as near-infrared probes for the detection of β-amyloid and tau fibrils. Chem Commun (Camb) 56:7269–7272
13.
Okamura N, Mori M, Furumoto S et al (2011) In vivo Detection of Amyloid Plaques in the Mouse Brain using the Near-Infrared Fluorescence Probe THK-265. J Alzheimers Dis 23:37–48CrossRefPubMed
14.
Schmidt A, Pahnke J (2012) Efficient near-infrared in vivo imaging of amyoid-β deposits in Alzheimer’s disease mouse models. J Alzheimers Dis 30:651–664
15.
Ergin A, Wang M, Zhang JY et al (2012) The feasibility of real-time in vivo optical detection of blood-brain barrier disruption with indocyanine green. J Neurooncol 106:551–560CrossRefPubMed
16.
van Dyck CH, Swanson CJ, Aisen P et al (2023) Lecanemab in Early Alzheimer’s Disease. New Engl J Med 388:9–21CrossRefPubMed
17.
Okamura N, Harada R, Ishiki A, Kikuchi A, Nakamura T, Kudo Y (2018) The development and validation of tau PET tracers: current status and future directions. Clin Transl Imaging 6:305–316CrossRefPubMedPubMedCentral
18.
Gyasi YI, Pang YP, Li XR, et al. (2020) Biological applications of near infrared fluorescence dye probes in monitoring Alzheimer’s disease. Eur J Med Chem 187:111982
19.
Zhang XL, Tian YL, Zhang C et al (2015) Near-infrared fluorescence molecular imaging of amyloid beta species and monitoring therapy in animal models of Alzheimer’s disease. P Natl Acad Sci USA 112:9734–9739CrossRef
20.
Ren WM, Zhang JJ, Peng C et al (2018) Fluorescent imaging of β-amyloid using BODIPY based near-infrared off-on fluorescent probe. Bioconjugate Chem 29:3459–3466
21.
Fu W, Yan CX, Guo ZQ et al (2019) Rational design of near-infrared aggregation-induced-emission- active probes: in situ mapping of amyloid-β plaques with ultrasensitivity and high-fidelity. J Am Chem Soc 141:3171–3177
22.
Hou SS, Yang JY, Lee JH et al (2023) Near-infrared fluorescence lifetime imaging of amyloid-β aggregates and tau fibrils through the intact skull of mice. Nat Biomed Eng 7:270–280
23.
24.
Ran C, Xu X, Raymond SB et al (2009) Design, synthesis, and testing of difluoroboron-derivatized curcumins as near-infrared probes for in vivo detection of amyloid-β deposits. J Am Chem Soc 131:15257–15261
25.
Watanabe H, Ono M, Matsumura K, Yoshimura M, Kimura H, Saji H (2013) Molecular imaging of β-amyloid plaques with near-infrared boron dipyrromethane (BODIPY)-based fluorescent probes. Mol Imaging 12:338–347
26.
Ono M, Ishikawa M, Kimura H et al (2010) Development of dual functional SPECT/fluorescent probes for imaging cerebral β-amyloid plaques. Bioorg Med Chem Lett 20:3885–3888
27.
Verwilst P, Kim HR, Seo J et al (2017) Rational Design of in Vivo Tau Tangle-Selective Near-Infrared Fluorophores: Expanding the BODIPY Universe. J Am Chem Soc 139:13393–13403CrossRefPubMed
Metadata
Title
A Novel Near-Infrared Fluorescence Probe THK-565 Enables In Vivo Detection of Amyloid Deposits in Alzheimer’s Disease Mouse Model
Authors
Fumito Naganuma
Daiki Murata
Marie Inoue
Yuri Maehori
Ryuichi Harada
Shozo Furumoto
Yukitsuka Kudo
Tadaho Nakamura
Nobuyuki Okamura
Publication date
14-08-2023
Publisher
Springer International Publishing
Published in
Molecular Imaging and Biology / Issue 6/2023
Print ISSN: 1536-1632
Electronic ISSN: 1860-2002
DOI
https://doi.org/10.1007/s11307-023-01843-4

Other articles of this Issue 6/2023

Molecular Imaging and Biology 6/2023 Go to the issue

Commentary

Imaging in Type 1 Diabetes, Current Perspectives and Directions

Review Article

Alpha Particle–Emitting Radiopharmaceuticals as Cancer Therapy: Biological Basis, Current Status, and Future Outlook for Therapeutics Discovery

Correction

Correction to: Magnetic Particle Imaging-Guided Hyperthermia for Precise Treatment of Cancer: Review, Challenges, and Prospects

Correction

Correction: High Vascular Delivery of EGF, but Low Receptor Binding Rate Is Observed in AsPC-1 Tumors as Compared to Normal Pancreas

Research Article

Urokinase-Type Plasminogen Activator Receptor (uPAR) Expression and [64Cu]Cu-DOTA-AE105 uPAR-PET/CT in Patient-Derived Xenograft Models of Oral Squamous Cell Carcinoma

Brief Article

Parametric Imaging of P-Glycoprotein Function at the Blood–Brain Barrier Using kE,brain-maps Generated from [11C]Metoclopramide PET Data in Rats, Nonhuman Primates and Humans