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
Research ArticleClinical Investigation

Detection of HER2-Low Lesions Using HER2-Targeted PET Imaging in Patients with Metastatic Breast Cancer: A Paired HER2 PET and Tumor Biopsy Analysis

Randy Yeh, Fresia Pareja, Parnian Shobeiri, Dara Ross, Vetri S. Jayaprakasam, Ali Aria Razmaria, Joshua Z. Drago, Audrey Mauguen, Serge K. Lyashchenko, Brian M. Zeglis, Jason S. Lewis and Gary A. Ulaner
Journal of Nuclear Medicine May 2025, jnumed.124.269227; DOI: https://doi.org/10.2967/jnumed.124.269227
Randy Yeh
1Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York;
2Department of Radiology, Weill Cornell Medical College, New York, New York;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Fresia Pareja
3Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Parnian Shobeiri
1Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Dara Ross
3Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York;
4Department of Pathology, Weill Cornell Medical College, New York, New York;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Vetri S. Jayaprakasam
1Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York;
2Department of Radiology, Weill Cornell Medical College, New York, New York;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ali Aria Razmaria
1Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York;
2Department of Radiology, Weill Cornell Medical College, New York, New York;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Joshua Z. Drago
5Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York;
6Department of Medicine, Weill Cornell Medical College, New York, New York;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Audrey Mauguen
7Department of Biostatistics and Epidemiology, Memorial Sloan Kettering Cancer Center, New York, New York;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Serge K. Lyashchenko
1Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York;
2Department of Radiology, Weill Cornell Medical College, New York, New York;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Brian M. Zeglis
1Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York;
2Department of Radiology, Weill Cornell Medical College, New York, New York;
8Department of Chemistry, Hunter College, New York, New York;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jason S. Lewis
1Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York;
2Department of Radiology, Weill Cornell Medical College, New York, New York;
9Program in Molecular Pharmacology, Memorial Sloan Kettering Cancer Center, New York, New York;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Gary A. Ulaner
1Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York;
10Molecular Imaging and Therapy, Hoag Family Cancer Institute, Newport Beach, California; and
11Departments of Radiology and Translational Genomics, University of Southern California, Los Angeles, California
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • PDF
Loading

Visual Abstract

Figure
  • Download figure
  • Open in new tab
  • Download powerpoint

Abstract

Trastuzumab deruxtecan (T-DXd), a human epidermal growth factor receptor 2 (HER2)–targeted antibody–drug conjugate, demonstrated remarkable efficacy in previously treated patients with HER2-low metastatic breast cancer (mBC), marking a new therapeutic option for this patient population. Prior studies with HER2 PET using 89Zr-radiolabeled antibodies were limited by high rates of imaging false positives for HER2-positive malignancy. In this retrospective study, we investigate whether these false positives (HER2-negative on pathology) could be explained by HER2-low lesions. Methods: A retrospective study was conducted of mBC patients who previously enrolled in 2 prospective HER2 PET imaging trials: NCT02286843 using 89Zr-trastuzumab and 89Zr-pertuzumab and NCT04692831 using 89Zr-ss-pertuzumab. Patients were included if paired HER2 PET scan and biopsy were performed within a 2-mo period. Of 56 total patients, 23 patients met the inclusion criteria. Pathology results for biopsied lesions were collected, without repeat interpretation, and lesions were classified as HER2-positive, HER2-low, or HER2-0. SUVmax of biopsied lesions were compared between pathologic classifications to determine whether lesion uptake intensity could differentiate between HER2-positive and HER2-low lesions. Results: All prior false-positive lesions on HER2 PET scans from NCT02286843 were reclassified as HER2-low (instead of HER2-negative). In the 89Zr-trastuzumab cohort, 3 lesions were HER2-positive (33%) and 6 were HER2-low (67%); in the 89Zr-pertuzumab cohort, 2 were HER2-positive (29%) and 5 were HER2-low (71%). In the 89Zr-ss-pertuzumab cohort (NCT04692831), 7 patients underwent recent biopsies of 8 total lesions demonstrating 1 HER2-positive (12%), 5 HER2-low (62%), and 2 HER2-0 lesions (25%). HER2 PET SUVmax of biopsied lesions were compared between HER2-positive and HER2-low lesions for the combination of all 3 radiotracer cohorts. HER2-low lesions had a significantly higher SUVmax (median, 12.7; interquartile range, 8.05) than did HER2-positive lesions (median, 6.4; interquartile range, 1.98; P = 0.01). Conclusion: HER2 PET imaging with 89Zr-radiolabeled antibodies detects HER2-low lesions in addition to HER2-positive lesions in patients with mBC, suggesting its ability to visualize the entire spectrum of HER2 expression. All prior false positives on 89Zr-trastuzumab and 89Zr-pertuzumab PET scans were reclassified as HER2-low. Lesion SUVmax is not reliable in differentiating HER2-positive from HER2-low lesions; however, it may be useful in distinguishing lesions expressing HER2 from HER2-0 lesions.

  • HER2
  • PET
  • breast cancer
  • pathology

Footnotes

  • Published online May 8, 2025.

  • © 2025 by the Society of Nuclear Medicine and Molecular Imaging.
View Full Text

This article requires a subscription to view the full text. If you have a subscription you may use the login form below to view the article. Access to this article can also be purchased.

SNMMI members

SNMMI Member Login

Login to the site using your SNMMI member credentials

Individuals

Non-Member Login

Login as an individual user

PreviousNext
Back to top

In this issue

Journal of Nuclear Medicine: 66 (5)
Journal of Nuclear Medicine
Vol. 66, Issue 5
May 1, 2025
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by author
  • Complete Issue (PDF)
Print
Download PDF
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.
Detection of HER2-Low Lesions Using HER2-Targeted PET Imaging in Patients with Metastatic Breast Cancer: A Paired HER2 PET and Tumor Biopsy Analysis
(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
Detection of HER2-Low Lesions Using HER2-Targeted PET Imaging in Patients with Metastatic Breast Cancer: A Paired HER2 PET and Tumor Biopsy Analysis
Randy Yeh, Fresia Pareja, Parnian Shobeiri, Dara Ross, Vetri S. Jayaprakasam, Ali Aria Razmaria, Joshua Z. Drago, Audrey Mauguen, Serge K. Lyashchenko, Brian M. Zeglis, Jason S. Lewis, Gary A. Ulaner
Journal of Nuclear Medicine May 2025, jnumed.124.269227; DOI: 10.2967/jnumed.124.269227

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
Detection of HER2-Low Lesions Using HER2-Targeted PET Imaging in Patients with Metastatic Breast Cancer: A Paired HER2 PET and Tumor Biopsy Analysis
Randy Yeh, Fresia Pareja, Parnian Shobeiri, Dara Ross, Vetri S. Jayaprakasam, Ali Aria Razmaria, Joshua Z. Drago, Audrey Mauguen, Serge K. Lyashchenko, Brian M. Zeglis, Jason S. Lewis, Gary A. Ulaner
Journal of Nuclear Medicine May 2025, jnumed.124.269227; DOI: 10.2967/jnumed.124.269227
Twitter logo Facebook logo LinkedIn logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One
Bookmark this article

Jump to section

  • Article
    • Visual Abstract
    • Abstract
    • MATERIALS AND METHODS
    • RESULTS
    • DISCUSSION
    • CONCLUSION
    • DISCLOSURE
    • Footnotes
    • REFERENCES
  • Figures & Data
  • Info & Metrics
  • PDF

Related Articles

  • No related articles found.
  • PubMed
  • Google Scholar

Cited By...

  • No citing articles found.
  • Google Scholar

More in this TOC Section

  • First-in-Human Study of 18F-Labeled PET Tracer for Glutamate AMPA Receptor [18F]K-40: A Derivative of [11C]K-2
  • [11C]Carfentanil PET Whole-Body Imaging of μ-Opioid Receptors: A First in-Human Study
Show more Clinical Investigation

Similar Articles

Keywords

  • HER2
  • PET
  • breast cancer
  • pathology
SNMMI

© 2025 SNMMI

Powered by HighWire