Skip to main content

Main menu

  • Home
  • Content
    • Current
    • Ahead of print
    • Past Issues
    • JNM Supplement
    • SNMMI Annual Meeting Abstracts
    • Continuing Education
    • JNM Podcasts
  • Subscriptions
    • Subscribers
    • Institutional and Non-member
    • Rates
    • Journal Claims
    • Corporate & Special Sales
  • Authors
    • Submit to JNM
    • Information for Authors
    • Assignment of Copyright
    • AQARA requirements
  • Info
    • Reviewers
    • Permissions
    • Advertisers
  • About
    • About Us
    • Editorial Board
    • Contact Information
  • More
    • Alerts
    • Feedback
    • Help
    • SNMMI Journals
  • SNMMI
    • JNM
    • JNMT
    • SNMMI Journals
    • SNMMI

User menu

  • Subscribe
  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
Journal of Nuclear Medicine
  • SNMMI
    • JNM
    • JNMT
    • SNMMI Journals
    • SNMMI
  • Subscribe
  • My alerts
  • Log in
  • My Cart
Journal of Nuclear Medicine

Advanced Search

  • Home
  • Content
    • Current
    • Ahead of print
    • Past Issues
    • JNM Supplement
    • SNMMI Annual Meeting Abstracts
    • Continuing Education
    • JNM Podcasts
  • Subscriptions
    • Subscribers
    • Institutional and Non-member
    • Rates
    • Journal Claims
    • Corporate & Special Sales
  • Authors
    • Submit to JNM
    • Information for Authors
    • Assignment of Copyright
    • AQARA requirements
  • Info
    • Reviewers
    • Permissions
    • Advertisers
  • About
    • About Us
    • Editorial Board
    • Contact Information
  • More
    • Alerts
    • Feedback
    • Help
    • SNMMI Journals
  • View or Listen to JNM Podcast
  • Visit JNM on Facebook
  • Join JNM on LinkedIn
  • Follow JNM on Twitter
  • Subscribe to our RSS feeds
Meeting ReportNeurosciences - Basic and Translational Neurosciences

[18F]MK6240 PET detects TAU in TgF344-AD rat brains

Baosheng Chen, William Mennie, Tutukhanim Balayeva, MingQiang Zheng, Chao Zheng, Feng Li, Jie Tong, Mingming Chen, Takuya Toyonaga, Richard Carson, Yiyun Huang and Zhengxin (Jason) Cai
Journal of Nuclear Medicine June 2024, 65 (supplement 2) 241584;
Baosheng Chen
1Yale New Haven Hospital, Attn: Receiving - New Haven, CT
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
William Mennie
2Yale University
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Tutukhanim Balayeva
3Yale School of Medicine - New Haven, CT
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
MingQiang Zheng
4Yale University PET Center
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Chao Zheng
5Yale University - New Haven, CT
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Feng Li
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jie Tong
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Mingming Chen
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Takuya Toyonaga
2Yale University
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Richard Carson
2Yale University
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yiyun Huang
2Yale University
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Zhengxin (Jason) Cai
6Yale School of Medicine
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
Loading

Abstract

241584

Introduction: The TgF344-AD rats express human mutant amyloid precursor protein (APPsw) and presenilin-1 (PS1ΔE9) and manifest cerebral amyloidosis, tauopathy, gliosis, apoptotic loss of neurons, and cognitive deficiency(1). [18F]FDDNP, the first PET tracer to visualize both amyloid plaques and tau tangles in living humans (2), exhibits uptake in the frontal cortices of 15-month-old TgF344-AD rats (1). Preliminary studies in humans and healthy mice using [18F]MK6240, the second-generation tau radiotracer demonstrated promising results with improved target specificity (3). So far, [18F]MK6240 has not been tested in AD animal models. In the present study, we explored the ability of [18F]MK6240 PET imaging to visualize tau tangles in the TgF344-AD rats.

Methods: TgF344-AD breeder rats were originally obtained from RRRC (University of Missouri) and mated in Yale Animal Resource Center to provide littermates for designated studies. [18F]MK6240 was produced in Yale PET center with a radiochemical purity of >99%. Female littermates (WT, n=4; AD, n=5) of 19 months old were scanned for 90 min using the FOCUS-220 scanner after [18F]MK6240 injection via the tail vein. Standard uptake value (SUV) curves were generated for brain regions (brain stem, hippocampus, limbic insular cortex, motor sensory cortex, striatum, cerebellum) and the whole brain. The striatum was used as the reference region to calculate SUV30-90 min and DVR using the simplified reference tissue model 2 (SRTM2). Immunohistochemical staining (IHC) was carried out in AD rat brain sections using rabbit anti-SV2A (1:1000) and mouse anti-Phospho-Tau (Ser202, Thr205; 1:200) antibody (Invitrogen) with ImmPRESS® Duet Double Staining Kit (Vector Lab). In vitro autoradiography (ARG) was carried out by incubating TgF344-AD brain slices (n=2 males; n=1 female; 20 um thickness/section) in 1x HEPES buffer (0.1% BSA) solution of [18F]MK6240 at room temperature for 30 min, followed by exposure to phosphor imaging plates. The plates were scanned, and images retrieved on the Typhoon 5 scanner. Data are presented as mean ± standard deviation (SD). Student t test was used to compare the differences.

Results: The average body weight of AD rats at ~19-month-old was ~ 16% heavier than the WT littermates (AD: 348.8±12.7 g; WT: 301.3±28.6 g). The average dosage/rat injected for AD and WT were 17.5±5.4 MBq and 14.2±2.7 MBq, respectively. There was no difference in administered activity dose between AD and WT groups (AD: 0.050 ±0.016 MBq/g; WT: 0.047±0.007 MBq/g; p=0.7). The tracer uptake peaked at ~ 3 min post tracer injection, quickly washed out within 20 min, and remained at the same level until the end of scan (Fig. 1A). Among the brain regions examined, cerebellum was found to have the increased SUV30-90 min (15%, p<0.05) and DVR (19%, p<0.05) in AD compared to WT rats (Fig. 1B, C; Table 1). SUV30-90 min correlated to DVR with an R2 of 0.83 (Fig. 1D). In addition, except for the hippocampus DVR (8%, p<0.05), all the other examined regions show a trend of increase in both SUV30-90 min and DVR values but didn’t reach the statistically significant difference. Importantly, in vitro ARG showed higher specific tracer uptake in the neocortex, cerebellum, and mid brain, but lower in the medulla, pons, and striatum of AD brains (Fig. 2A, B). Further, Tau IHC staining results confirmed the findings from both the PET imaging and in vitro ARG (Fig. 2C).

Conclusions: Conclusion: Our data suggest that at age of 19-month-old, the female TgF344-AD rats have widespread expression of phospho-Tau proteins in their brains. Our result supports the use of [18F]MK6240 for tau imaging in TgF344-AD rats in future studies.

References

1. Cohen RM, et al. J Neurosci. 2013;33:6245-6256.

2. Shin J, et al. J Alzheimers Dis. 2011;26 Suppl 3:135-145.

3. Bao W, et al. Front Aging Neurosci. 2021;13:624330.

Figure
  • Download figure
  • Open in new tab
  • Download powerpoint
Figure
  • Download figure
  • Open in new tab
  • Download powerpoint
Previous
Back to top

In this issue

Journal of Nuclear Medicine
Vol. 65, Issue supplement 2
June 1, 2024
  • Table of Contents
  • Index by author
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for your interest in spreading the word on Journal of Nuclear Medicine.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
[18F]MK6240 PET detects TAU in TgF344-AD rat brains
(Your Name) has sent you a message from Journal of Nuclear Medicine
(Your Name) thought you would like to see the Journal of Nuclear Medicine web site.
Citation Tools
[18F]MK6240 PET detects TAU in TgF344-AD rat brains
Baosheng Chen, William Mennie, Tutukhanim Balayeva, MingQiang Zheng, Chao Zheng, Feng Li, Jie Tong, Mingming Chen, Takuya Toyonaga, Richard Carson, Yiyun Huang, Zhengxin (Jason) Cai
Journal of Nuclear Medicine Jun 2024, 65 (supplement 2) 241584;

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
[18F]MK6240 PET detects TAU in TgF344-AD rat brains
Baosheng Chen, William Mennie, Tutukhanim Balayeva, MingQiang Zheng, Chao Zheng, Feng Li, Jie Tong, Mingming Chen, Takuya Toyonaga, Richard Carson, Yiyun Huang, Zhengxin (Jason) Cai
Journal of Nuclear Medicine Jun 2024, 65 (supplement 2) 241584;
Twitter logo Facebook logo LinkedIn logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One
Bookmark this article

Jump to section

  • Article
  • Figures & Data
  • Info & Metrics

Related Articles

  • No related articles found.
  • Google Scholar

Cited By...

  • No citing articles found.
  • Google Scholar

More in this TOC Section

  • Early detection and tracking of activated macrophages and microglia in a mouse model of multiple sclerosis using [18F]OP-801 PET imaging before and after a novel immunomodulatory drug
  • Investigating Neuromodulatory Effects of rTMS and Their Stimulation Parameter Dependence in the NHP Model
  • Tributyrin Supplementation Increases Brain Butyrate Availability and Improves Parkinson’s Disease Motor Symptoms
Show more Neurosciences - Basic and Translational Neurosciences

Similar Articles

SNMMI

© 2025 SNMMI

Powered by HighWire