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

Effect of Tumor Perfusion and Receptor Density on Tumor Control Probability in 177Lu-DOTATATE Therapy: An In Silico Analysis for Standard and Optimized Treatment

Luis David Jiménez-Franco, Gerhard Glatting, Vikas Prasad, Wolfgang A. Weber, Ambros J. Beer and Peter Kletting
Journal of Nuclear Medicine January 2021, 62 (1) 92-98; DOI: https://doi.org/10.2967/jnumed.120.245068
Luis David Jiménez-Franco
1ABX-CRO Advanced Pharmaceutical Services Forschungsgesellschaft mbH, Dresden, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Gerhard Glatting
2Department of Nuclear Medicine, Ulm University, Ulm, Germany
3Medical Radiation Physics, Department of Nuclear Medicine, Ulm University, Ulm, Germany; and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Vikas Prasad
2Department of Nuclear Medicine, Ulm University, Ulm, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Wolfgang A. Weber
4Department of Nuclear Medicine, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ambros J. Beer
2Department of Nuclear Medicine, Ulm University, Ulm, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Peter Kletting
2Department of Nuclear Medicine, Ulm University, Ulm, Germany
3Medical Radiation Physics, Department of Nuclear Medicine, Ulm University, Ulm, Germany; and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Supplemental
  • Info & Metrics
  • PDF
Loading

Abstract

The aim of this work was to determine a minimal tumor perfusion and receptor density for 177Lu-DOTATATE therapy using physiologically based pharmacokinetic (PBPK) modeling considering, first, a desired tumor control probability (TCP) of 99% and, second, a maximal tolerated biologically effective dose (BEDmax) for organs at risk (OARs) in the treatment of neuroendocrine tumors and meningioma. Methods: A recently developed PBPK model was used. Nine virtual patients (i.e., individualized PBPK models) were used to perform simulations of pharmacokinetics for different combinations of perfusion (0.001–0.1 mL/g/min) and receptor density (1–100 nmol/L). The TCP for each combination was determined for 3 different treatment strategies: a standard treatment (4 cycles of 7.4 GBq and 105 nmol), a treatment maximizing the number of cycles based on BEDmax for red marrow and kidneys, and a treatment having 4 cycles with optimized ligand amount and activity. The red marrow and the kidneys (BEDmax of 2 Gy15 and 40 Gy2.5, respectively) were assumed to be OARs. Additionally, the influence of varying glomerular filtration rates, kidney somatostatin receptor densities, tumor volumes, and release rates was investigated. Results: To achieve a TCP of at least 99% in the standard treatment, a minimal tumor perfusion of 0.036 ± 0.023 mL/g/min and receptor density of 34 ± 20 nmol/L were determined for the 9 virtual patients. With optimization of the number of cycles, the minimum values for perfusion and receptor density were considerably lower, at 0.022 ± 0.012 mL/g/min and 21 ± 11 nmol/L, respectively. However, even better results (perfusion, 0.018 ± 0.009 mL/g/min; receptor density, 18 ± 10 nmol/L) were obtained for strategy 3. The release rate of 177Lu (or labeled metabolites) from tumor cells had the strongest effect on the minimal perfusion and receptor density for standard and optimized treatments. Conclusion: PBPK modeling and simulations represent an elegant approach to individually determine the minimal tumor perfusion and minimal receptor density required to achieve an adequate TCP. This computational method can be used in the radiopharmaceutical development process for ligand and target selection for specific types of tumors. In addition, this method could be used to optimize clinical trials.

  • minimal tumor perfusion
  • minimal receptor density
  • PBPK modeling
  • tumor control probability
  • 177Lu-DOTATATE

Footnotes

  • Published online Jul. 9, 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 (1)
Journal of Nuclear Medicine
Vol. 62, Issue 1
January 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.
Effect of Tumor Perfusion and Receptor Density on Tumor Control Probability in 177Lu-DOTATATE Therapy: An In Silico Analysis for Standard and Optimized Treatment
(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
Effect of Tumor Perfusion and Receptor Density on Tumor Control Probability in 177Lu-DOTATATE Therapy: An In Silico Analysis for Standard and Optimized Treatment
Luis David Jiménez-Franco, Gerhard Glatting, Vikas Prasad, Wolfgang A. Weber, Ambros J. Beer, Peter Kletting
Journal of Nuclear Medicine Jan 2021, 62 (1) 92-98; DOI: 10.2967/jnumed.120.245068

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
Effect of Tumor Perfusion and Receptor Density on Tumor Control Probability in 177Lu-DOTATATE Therapy: An In Silico Analysis for Standard and Optimized Treatment
Luis David Jiménez-Franco, Gerhard Glatting, Vikas Prasad, Wolfgang A. Weber, Ambros J. Beer, Peter Kletting
Journal of Nuclear Medicine Jan 2021, 62 (1) 92-98; DOI: 10.2967/jnumed.120.245068
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
    • Abstract
    • MATERIALS AND METHODS
    • RESULTS
    • DISCUSSION
    • CONCLUSION
    • DISCLOSURE
    • Footnotes
    • REFERENCES
  • Figures & Data
  • Supplemental
  • 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

  • Assessing Response to [177Lu]PSMA Radioligand Therapy using modified PSMA PET Progression Criteria
  • 177Lu-Labeled Albumin-Binder–Conjugated PSMA-Targeting Agents with Extremely High Tumor Uptake and Enhanced Tumor-to-Kidney Absorbed Dose Ratio
  • High Interobserver Agreement for the Standardized Reporting System SSTR-RADS 1.0 on Somatostatin Receptor PET/CT
Show more Theranostics

Basic

  • Quantification of Macrophage-Driven Inflammation During Myocardial Infarction with 18F-LW223, a Novel TSPO Radiotracer with Binding Independent of the rs6971 Human Polymorphism
  • Longitudinal Molecular Imaging of Progesterone Receptor Reveals Early Differential Response to Endocrine Therapy in Breast Cancer with an Activating ESR1 Mutation
  • 177Lu-Labeled Albumin-Binder–Conjugated PSMA-Targeting Agents with Extremely High Tumor Uptake and Enhanced Tumor-to-Kidney Absorbed Dose Ratio
Show more Basic

Similar Articles

Keywords

  • minimal tumor perfusion
  • minimal receptor density
  • PBPK modeling
  • tumor control probability
  • 177Lu-dotatate
SNMMI

© 2021 Journal of Nuclear Medicine

Powered by HighWire