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 ReportMolecular Targeting Probes - Radioactive & Nonradioactive

Enhancing Tumor Uptake for 177Lu-Labeled MC1R Targeting Radioligands by Combining N-Methylations with an Albumin Binder

Chengcheng Zhang, Zhengxing Zhang, Jutta Zeisler, Nadine Colpo, Kuo-Shyan Lin and Francois Benard
Journal of Nuclear Medicine May 2020, 61 (supplement 1) 378;
Chengcheng Zhang
1BC Cancer Research Centre Vancouver BC Canada
4BC Cancer Research Centre Vancouver BC Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Zhengxing Zhang
2BC Cancer Agency Vancouver BC Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jutta Zeisler
3Cancer Research Center Vancouver BC Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Nadine Colpo
1BC Cancer Research Centre Vancouver BC Canada
4BC Cancer Research Centre Vancouver BC Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kuo-Shyan Lin
5BC Cancer Agency Vancouver BC
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Francois Benard
6BC Cancer Agency Research Centre Vancouver BC
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Info & Metrics
Loading

Abstract

378

Objectives: Radiotracers derived from Melanotan II (MTII), a melanocortin-1 receptor (MC1R) targeting peptide, have been proposed for melanoma imaging and radionuclide therapy. We previously reported CCZ01048, an MTII derivative which showed excellent imaging properties with 68Ga at early time points. However, when radiolabeled with 177Lu, moderate tumor uptake was observed at longer time points, due to the sub-optimal in vivo stability. The aim of this study was to evaluate a panel of novel N-methylated MTIIderivatives for their binding affinity and stability, and characterize the top candidate, conjugated with an albumin binder, for tumor uptake in a preclinical model of melanoma.

Methods: The peptides were prepared by Fmoc solid phase synthesis. N-methylation was performed under Mitsunobu conditions. The DOTA-containing peptides were synthesized with one to four N-methylations on the His, Arg, Trp and Lys residues of CCZ01048. For the derivatives conjugated with an albumin binder, Fmoc-Lys(Mtt)-OH, Fmoc-Glu(OtBu)-OH and 4-(p-iodophenyl)butyric acid were used before coupling DOTA chelator. Receptor binding affinity was measured using in vitro competition binding assays on B16F10 cells. The peptides were radiolabeled with 68Ga, and their in vivo stability was performed via radio-HPLC using urine samples at 1 h post-injection (p.i.) from C57BL/6J mice. The top candidate was conjugated with the albumin binder and radiolabeled with 177Lu. SPECT/CT imaging and biodistribution studies were performed using 177Lu-labeled peptides in C57BL/6J mice bearing B16F10 tumors.

Results: A panel of six novel MTII derivatives were synthesized with one to four N-methylations, which had a positive impact on their stability, with average in vivo urine stability ranging from 41.4% to ≥ 98% (n ≥ 3), compared to [68Ga]Ga-CCZ01048 at 34%. The N-methylations had an unfavorable impact on binding affinity, with average inhibition constants ranging from 1.5 to 35.9 nM (n ≥ 3), compared to 0.31 nM for natGa-CCZ01048. The best candidate was CCZ01106, which had improved stability (82.5%) while maintaining excellent binding affinity (1.5 nM). An albumin binder was conjugated to CCZ01106 to afford CCZ01118. 177Lu-labeled CCZ01118 was evaluated in B16F10 tumor-bearing C57BL/6J mice at 1, 4, 24 and 120 h p.i., and the tumor uptake was 24.44 ± 1.76, 29.70 ± 5.23, 18.35 ± 1.35, and 2.63 ± 0.21 percent injected dose per gram of tissue (%ID/g), respectively (n = 5). This was a significant improvement over 177Lu-labeled CCZ01048 with respective tumor uptake values of 16.28 ± 3.75, 16.71 ± 3.86, 4.39 ± 1.36, and 0.41 ± 0.21%ID/g at the same time points[FB1] . SPECT imaging also showed consistent findings as much higher radioactivity accumulation was visualized in tumors. Conclusion: With the addition of N-methylations and an albumin binder, we designed CCZ01118, which showed greatly enhanced tumor uptake with 177Lu in SPECT imaging and biodistribution studies. CCZ01118 is therefore a promising compound for radionuclide therapy of melanoma.

Previous
Back to top

In this issue

Journal of Nuclear Medicine
Vol. 61, Issue supplement 1
May 1, 2020
  • 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.
Enhancing Tumor Uptake for 177Lu-Labeled MC1R Targeting Radioligands by Combining N-Methylations with an Albumin Binder
(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
Enhancing Tumor Uptake for 177Lu-Labeled MC1R Targeting Radioligands by Combining N-Methylations with an Albumin Binder
Chengcheng Zhang, Zhengxing Zhang, Jutta Zeisler, Nadine Colpo, Kuo-Shyan Lin, Francois Benard
Journal of Nuclear Medicine May 2020, 61 (supplement 1) 378;

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
Enhancing Tumor Uptake for 177Lu-Labeled MC1R Targeting Radioligands by Combining N-Methylations with an Albumin Binder
Chengcheng Zhang, Zhengxing Zhang, Jutta Zeisler, Nadine Colpo, Kuo-Shyan Lin, Francois Benard
Journal of Nuclear Medicine May 2020, 61 (supplement 1) 378;
Twitter logo Facebook logo LinkedIn logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One
Bookmark this article

Jump to section

  • Article
  • Info & Metrics

Related Articles

  • No related articles found.
  • Google Scholar

Cited By...

  • No citing articles found.
  • Google Scholar

More in this TOC Section

Molecular Targeting Probes - Radioactive & Nonradioactive

  • SPECT and PET imaging of CD11b-positive immune cells in an orthotopic mouse model of glioma with Zr-89 and Lu-177 labeled Lumi804-anti-CD11b antibody
  • ‘In-loop’ [11C]CO2fixation: Application to the synthesis of a 11C-labeled cholesterol 24-hydroxylase inhibitor
  • N-(Maleimidoethyl)-3-(guanidinomethyl)-5-[131I]iodobenzmide ([131I]MEGMIB): A Residualizing Prosthetic Agent for Site-Specific Radioiodination of Internalizing Single Domain Antibody Fragments.
Show more Molecular Targeting Probes - Radioactive & Nonradioactive

Preclinical Probes for Oncology I

  • GD2/B7-H3 bispecific antibodies for next-generation neuroblastoma treatment
  • Multimodality PET/CT and NIRF imaging for image-guided photothermal therapy of colon cancer with exosomes based nanoprobe
Show more Preclinical Probes for Oncology I

Similar Articles

SNMMI

© 2025 SNMMI

Powered by HighWire