Skip to main content

Main menu

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

Multimodal Imaging of 2-Cycle PRRT with 177Lu-DOTA-JR11 and 177Lu-DOTATOC in an Orthotopic Neuroendocrine Xenograft Tumor Mouse Model

Jakob Albrecht, Samantha Exner, Carsten Grötzinger, Sonal Prasad, Frank Konietschke, Nicola Beindorff, Anja A. Kühl, Vikas Prasad, Winfried Brenner and Eva J. Koziolek
Journal of Nuclear Medicine March 2021, 62 (3) 393-398; DOI: https://doi.org/10.2967/jnumed.120.250274
Jakob Albrecht
1Department of Nuclear Medicine, Charité–Universitätsmedizin Berlin, Berlin, Germany
2German Cancer Consortium, Berlin, Germany
3German Cancer Research Center, Heidelberg, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Samantha Exner
4Department of Hepatology and Gastroenterology, Charité–Universitätsmedizin Berlin, Berlin, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Carsten Grötzinger
2German Cancer Consortium, Berlin, Germany
3German Cancer Research Center, Heidelberg, Germany
4Department of Hepatology and Gastroenterology, Charité–Universitätsmedizin Berlin, Berlin, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sonal Prasad
1Department of Nuclear Medicine, Charité–Universitätsmedizin Berlin, Berlin, Germany
5Berlin Experimental Radionuclide Imaging Center, Charité–Universitätsmedizin Berlin, Berlin, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Frank Konietschke
6Institute of Biometry and Clinical Epidemiology, Charité–Universitätsmedizin Berlin, Berlin, Germany
7Berlin Institute of Health, Berlin, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Nicola Beindorff
5Berlin Experimental Radionuclide Imaging Center, Charité–Universitätsmedizin Berlin, Berlin, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Anja A. Kühl
8iPATH.Berlin–Immunopathology for Experimental Models, Charité–Universitätsmedizin Berlin; and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Vikas Prasad
1Department of Nuclear Medicine, Charité–Universitätsmedizin Berlin, Berlin, Germany
9Department of Nuclear Medicine, University Hospital Ulm, Ulm, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Winfried Brenner
1Department of Nuclear Medicine, Charité–Universitätsmedizin Berlin, Berlin, Germany
2German Cancer Consortium, Berlin, Germany
5Berlin Experimental Radionuclide Imaging Center, Charité–Universitätsmedizin Berlin, Berlin, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Eva J. Koziolek
1Department of Nuclear Medicine, Charité–Universitätsmedizin Berlin, Berlin, Germany
2German Cancer Consortium, Berlin, Germany
3German Cancer Research Center, Heidelberg, Germany
  • 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

Figure1
  • Download figure
  • Open in new tab
  • Download powerpoint

Abstract

Peptide receptor radionuclide therapy (PRRT) using radiolabeled somatostatin receptor (SSTR) analogs is a common approach in advanced neuroendocrine neoplasms. Recently, SSTR antagonists have shown promising results for imaging and therapy due to a higher number of binding sites than in commonly used agonists. We evaluated PRRT with SSTR agonist 177Lu-DOTATOC and antagonist 177Lu-DOTA-JR11 longitudinally in an orthotopic murine pancreatic neuroendocrine neoplasm model expressing human SSTR2. Morphologic and metabolic changes during treatment were assessed using multimodal imaging, including hybrid PET/MRI and SPECT/CT. Methods: In vitro radioligand binding and internalization assays and cell-cycle analysis were performed. SSTR2-transfected BON cells (BON-SSTR2) were used for in vivo experiments. Tumor-bearing mice received 2 intravenous injections of 100 μL of saline, 30 MBq of 177Lu-DOTATOC, or 20 MBq of 177Lu-DOTA-JR11 with an interval of 3 wk. Weekly T2-weighted MRI was performed for tumor monitoring. Viability of the tumor tissue was assessed by 18F-FDG PET/MRI once after PRRT. Tumor and kidney uptake of the respective radiopharmaceuticals was measured 24 h after injection by SPECT/CT. Results: Compared with 177Lu-DOTATOC, 177Lu-DOTA-JR11 treatment resulted in an increased accumulation of cells in G2/M phase. Animals treated with the SSTR antagonist showed a significant reduction in tumor size (P < 0.001) and an increased median survival (207 d; interquartile range [IQR], 132–228) compared with 177Lu-DOTATOC (126 d; IQR, 118–129). SPECT/CT revealed a 4-fold higher median tumor uptake for the antagonist and a 3-fold higher tumor-to-kidney ratio in the first treatment cycle. During the second therapy cycle, tumor uptake of 177Lu-DOTATOC was significantly lower (P = 0.01) whereas 177Lu-DOTA-JR11 uptake remained stable. Imaging of tumor morphology indicated comparatively larger necrotic fractions for 177Lu-DOTA-JR11 despite further tumor growth. These results were confirmed by 18F-FDG PET, revealing the least amount of viable tumor tissue in 177Lu-DOTA-JR11–treated animals, at 6.2% (IQR, 2%–23%). Conclusion: 177Lu-DOTA-JR11 showed a higher tumor-to-kidney ratio and a more pronounced cytotoxic effect than did 177Lu-DOTATOC. Additionally, tumor uptake was more stable over the course of 2 treatment cycles.

  • 177Lu-DOTA-JR11
  • multimodal imaging
  • PET/MRI
  • somatostatin receptor antagonist
  • peptide receptor radionuclide therapy
  • SPECT/CT

Footnotes

  • Published online Aug. 28, 2020.

  • © 2021 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: 62 (3)
Journal of Nuclear Medicine
Vol. 62, Issue 3
March 1, 2021
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by author
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.
Multimodal Imaging of 2-Cycle PRRT with 177Lu-DOTA-JR11 and 177Lu-DOTATOC in an Orthotopic Neuroendocrine Xenograft Tumor Mouse Model
(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
Multimodal Imaging of 2-Cycle PRRT with 177Lu-DOTA-JR11 and 177Lu-DOTATOC in an Orthotopic Neuroendocrine Xenograft Tumor Mouse Model
Jakob Albrecht, Samantha Exner, Carsten Grötzinger, Sonal Prasad, Frank Konietschke, Nicola Beindorff, Anja A. Kühl, Vikas Prasad, Winfried Brenner, Eva J. Koziolek
Journal of Nuclear Medicine Mar 2021, 62 (3) 393-398; DOI: 10.2967/jnumed.120.250274

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
Multimodal Imaging of 2-Cycle PRRT with 177Lu-DOTA-JR11 and 177Lu-DOTATOC in an Orthotopic Neuroendocrine Xenograft Tumor Mouse Model
Jakob Albrecht, Samantha Exner, Carsten Grötzinger, Sonal Prasad, Frank Konietschke, Nicola Beindorff, Anja A. Kühl, Vikas Prasad, Winfried Brenner, Eva J. Koziolek
Journal of Nuclear Medicine Mar 2021, 62 (3) 393-398; DOI: 10.2967/jnumed.120.250274
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

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

Related Articles

  • This Month in JNM
  • PubMed
  • Google Scholar

Cited By...

  • No citing articles found.
  • Google Scholar

More in this TOC Section

Theranostics

  • Peptide Receptor Radionuclide Therapy of Late-Stage Neuroendocrine Tumor Patients with Multiple Cycles of 177Lu-DOTA-EB-TATE
  • Dissimilar DNA Damage to Blood Lymphocytes After 177Lu-Labeled DOTATOC or Prostate-Specific Membrane Antigen Therapy
Show more Theranostics

Basic

  • Immuno-PET Detects Changes in Multi-RTK Tumor Cell Expression Levels in Response to Targeted Kinase Inhibition
  • Noninvasive Evaluation of CD20 Expression Using 64Cu-Labeled F(ab′)2 Fragments of Obinutuzumab in Lymphoma
Show more Basic

Similar Articles

Keywords

  • 177Lu-DOTA-JR11
  • multimodal imaging
  • PET/MRI
  • somatostatin receptor antagonist
  • peptide receptor radionuclide therapy
  • SPECT/CT
SNMMI

© 2021 Journal of Nuclear Medicine

Powered by HighWire