Imaging Aβ Plaques in Living Transgenic Mice with Multiphoton Microscopy and Methoxy-X04, a Systemically Administered Congo Red Derivative (original) (raw)

Journal Article

,

William E. Klunk, MD, PhD

Laboratory of Molecular Neuropharmacology, Department of Psychiatry (WEK, MLD), University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; Alzheimer's Research Unit (BJB, STK, MEL, BTH), Massachusetts General Hospital, Charlestown, Massachusetts; PET Facility, Department of Radiology (CAM, DPH, YW), University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; Center for Neurologic Diseases, Department of Pathology (MPF), Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.

Correspondence to: William E. Klunk, MD, PhD, University of Pittsburgh, 705 Parran Hall-GSPH, 130 DeSoto Street, Pittsburgh, PA 15213.

Search for other works by this author on:

,

Laboratory of Molecular Neuropharmacology, Department of Psychiatry (WEK, MLD), University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; Alzheimer's Research Unit (BJB, STK, MEL, BTH), Massachusetts General Hospital, Charlestown, Massachusetts; PET Facility, Department of Radiology (CAM, DPH, YW), University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; Center for Neurologic Diseases, Department of Pathology (MPF), Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.

Search for other works by this author on:

,

Laboratory of Molecular Neuropharmacology, Department of Psychiatry (WEK, MLD), University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; Alzheimer's Research Unit (BJB, STK, MEL, BTH), Massachusetts General Hospital, Charlestown, Massachusetts; PET Facility, Department of Radiology (CAM, DPH, YW), University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; Center for Neurologic Diseases, Department of Pathology (MPF), Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.

Search for other works by this author on:

,

Laboratory of Molecular Neuropharmacology, Department of Psychiatry (WEK, MLD), University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; Alzheimer's Research Unit (BJB, STK, MEL, BTH), Massachusetts General Hospital, Charlestown, Massachusetts; PET Facility, Department of Radiology (CAM, DPH, YW), University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; Center for Neurologic Diseases, Department of Pathology (MPF), Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.

Search for other works by this author on:

,

Laboratory of Molecular Neuropharmacology, Department of Psychiatry (WEK, MLD), University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; Alzheimer's Research Unit (BJB, STK, MEL, BTH), Massachusetts General Hospital, Charlestown, Massachusetts; PET Facility, Department of Radiology (CAM, DPH, YW), University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; Center for Neurologic Diseases, Department of Pathology (MPF), Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.

Search for other works by this author on:

,

Matthew P. Frosch, MD, PhD

Laboratory of Molecular Neuropharmacology, Department of Psychiatry (WEK, MLD), University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; Alzheimer's Research Unit (BJB, STK, MEL, BTH), Massachusetts General Hospital, Charlestown, Massachusetts; PET Facility, Department of Radiology (CAM, DPH, YW), University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; Center for Neurologic Diseases, Department of Pathology (MPF), Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.

Search for other works by this author on:

,

Laboratory of Molecular Neuropharmacology, Department of Psychiatry (WEK, MLD), University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; Alzheimer's Research Unit (BJB, STK, MEL, BTH), Massachusetts General Hospital, Charlestown, Massachusetts; PET Facility, Department of Radiology (CAM, DPH, YW), University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; Center for Neurologic Diseases, Department of Pathology (MPF), Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.

Search for other works by this author on:

,

Laboratory of Molecular Neuropharmacology, Department of Psychiatry (WEK, MLD), University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; Alzheimer's Research Unit (BJB, STK, MEL, BTH), Massachusetts General Hospital, Charlestown, Massachusetts; PET Facility, Department of Radiology (CAM, DPH, YW), University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; Center for Neurologic Diseases, Department of Pathology (MPF), Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.

Search for other works by this author on:

,

Laboratory of Molecular Neuropharmacology, Department of Psychiatry (WEK, MLD), University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; Alzheimer's Research Unit (BJB, STK, MEL, BTH), Massachusetts General Hospital, Charlestown, Massachusetts; PET Facility, Department of Radiology (CAM, DPH, YW), University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; Center for Neurologic Diseases, Department of Pathology (MPF), Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.

Search for other works by this author on:

Bradley T. Hyman, MD, PhD

Laboratory of Molecular Neuropharmacology, Department of Psychiatry (WEK, MLD), University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; Alzheimer's Research Unit (BJB, STK, MEL, BTH), Massachusetts General Hospital, Charlestown, Massachusetts; PET Facility, Department of Radiology (CAM, DPH, YW), University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; Center for Neurologic Diseases, Department of Pathology (MPF), Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.

Search for other works by this author on:

Received:

08 February 2002

Revision received:

20 May 2002

Published:

01 September 2002

• • Article contents
  • Figures & tables
  • Video
  • Audio
  • Supplementary Data
• Cite

Cite

William E. Klunk, Brian J. Bacskai, Chester A. Mathis, Stephen T. Kajdasz, Megan E. McLellan, Matthew P. Frosch, Manik L. Debnath, Daniel P. Holt, Yanming Wang, Bradley T. Hyman, Imaging Aβ Plaques in Living Transgenic Mice with Multiphoton Microscopy and Methoxy-X04, a Systemically Administered Congo Red Derivative, Journal of Neuropathology & Experimental Neurology, Volume 61, Issue 9, September 2002, Pages 797–805, https://doi.org/10.1093/jnen/61.9.797
Close

Navbar Search Filter Mobile Enter search term Search

Abstract

The identification of amyloid deposits in living Alzheimer disease (AD) patients is important for both early diagnosis and for monitoring the efficacy of newly developed anti-amyloid therapies. Methoxy-X04 is a derivative of Congo red and Chrysamine-G that contains no acid groups and is therefore smaller and much more lipophilic than Congo red or Chrysamine-G. Methoxy-X04 retains in vitro binding affinity for amyloid β (Aβ) fibrils (Ki = 26.8 nM) very similar to that of Chrysamine-G (Ki = 25.3 nM). Methoxy-X04 is fluorescent and stains plaques, tangles, and cerebrovascular amyloid in postmortem sections of AD brain with good specificity. Using multiphoton microscopy to obtain high-resolution (1 μm) fluorescent images from the brains of living PS1/APP mice, individual plaques could be distinguished within 30 to 60 min after a single i.v. injection of 5 to 10 mg/kg methoxy-X04. A single i.p. injection of 10 mg/kg methoxy-X04 also produced high contrast images of plaques and cerebrovascular amyloid in PS1/APP mouse brain. Complementary quantitative studies using tracer doses of carbon-11-labeled methoxy-X04 show that it enters rat brain in amounts that suggest it is a viable candidate as a positron emission tomography (PET) amyloid-imaging agent for in vivo human studies.

Copyright © 2002 by the American Association of Neuropathologists

Topic:

• amyloid
• positron-emission tomography
• autopsy
• congo red
• mechlorethamine
• mice, transgenic
• new mexico
• brain
• diagnostic imaging
• mice
• rats
• affinity
• fibril

You do not currently have access to this article.

Personal account

• Sign in with email/username & password
• Get email alerts
• Save searches
• Purchase content
• Activate your purchase/trial code
• Add your ORCID iD

Get help with access

Institutional access

Access to content on Oxford Academic is often provided through institutional subscriptions and purchases. If you are a member of an institution with an active account, you may be able to access content in one of the following ways:

IP based access

Typically, access is provided across an institutional network to a range of IP addresses. This authentication occurs automatically, and it is not possible to sign out of an IP authenticated account.

Sign in through your institution

Choose this option to get remote access when outside your institution. Shibboleth/Open Athens technology is used to provide single sign-on between your institution’s website and Oxford Academic.

1. Click Sign in through your institution.
2. Select your institution from the list provided, which will take you to your institution's website to sign in.
3. When on the institution site, please use the credentials provided by your institution. Do not use an Oxford Academic personal account.
4. Following successful sign in, you will be returned to Oxford Academic.

If your institution is not listed or you cannot sign in to your institution’s website, please contact your librarian or administrator.

Sign in with a library card

Enter your library card number to sign in. If you cannot sign in, please contact your librarian.

Society Members

Society member access to a journal is achieved in one of the following ways:

Sign in through society site

Many societies offer single sign-on between the society website and Oxford Academic. If you see ‘Sign in through society site’ in the sign in pane within a journal:

1. Click Sign in through society site.
2. When on the society site, please use the credentials provided by that society. Do not use an Oxford Academic personal account.
3. Following successful sign in, you will be returned to Oxford Academic.

If you do not have a society account or have forgotten your username or password, please contact your society.

Sign in using a personal account

Some societies use Oxford Academic personal accounts to provide access to their members. See below.

Personal account

A personal account can be used to get email alerts, save searches, purchase content, and activate subscriptions.

Some societies use Oxford Academic personal accounts to provide access to their members.

Viewing your signed in accounts

Click the account icon in the top right to:

• View your signed in personal account and access account management features.
• View the institutional accounts that are providing access.

Signed in but can't access content

Oxford Academic is home to a wide variety of products. The institutional subscription may not cover the content that you are trying to access. If you believe you should have access to that content, please contact your librarian.

Institutional account management

For librarians and administrators, your personal account also provides access to institutional account management. Here you will find options to view and activate subscriptions, manage institutional settings and access options, access usage statistics, and more.

Purchase

Short-term Access

To purchase short-term access, please sign in to your personal account above.

Don't already have a personal account? Register

Imaging Aβ Plaques in Living Transgenic Mice with Multiphoton Microscopy and Methoxy-X04, a Systemically Administered Congo Red Derivative - 24 Hours access

EUR €38.00

GBP £33.00

USD $41.00

Rental

This article is also available for rental through DeepDyve.

Citations

Views

Altmetric

Metrics

Total Views 11,529

8,414 Pageviews

3,115 PDF Downloads

Since 1/1/2017

Citations

328 Web of Science

×

Email alerts

Citing articles via

• Latest

• Most Read

• Most Cited

More from Oxford Academic