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 Investigations

Analysis of 177Lu-DOTA-Octreotate Therapy–Induced DNA Damage in Peripheral Blood Lymphocytes of Patients with Neuroendocrine Tumors

Delphine Denoyer, Pavel Lobachevsky, Price Jackson, Mick Thompson, Olga A. Martin and Rodney J. Hicks
Journal of Nuclear Medicine April 2015, 56 (4) 505-511; DOI: https://doi.org/10.2967/jnumed.114.145581
Delphine Denoyer
1Molecular Imaging and Targeted Therapeutics, Translational Research Laboratory, Peter MacCallum Cancer Centre, Melbourne, Australia
2Centre for Cellular and Molecular Biology, Deakin University, Burwood, Australia
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Pavel Lobachevsky
3Molecular Radiation Biology Laboratory, Peter MacCallum Cancer Centre, Melbourne, Australia
4Sir Peter MacCallum Department of Oncology, University of Melbourne, Australia; and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Price Jackson
5Division of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, Melbourne, Australia.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Mick Thompson
5Division of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, Melbourne, Australia.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Olga A. Martin
3Molecular Radiation Biology Laboratory, Peter MacCallum Cancer Centre, Melbourne, Australia
4Sir Peter MacCallum Department of Oncology, University of Melbourne, Australia; and
5Division of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, Melbourne, Australia.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Rodney J. Hicks
1Molecular Imaging and Targeted Therapeutics, Translational Research Laboratory, Peter MacCallum Cancer Centre, Melbourne, Australia
4Sir Peter MacCallum Department of Oncology, University of Melbourne, Australia; and
5Division of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, Melbourne, Australia.
  • 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

Article Figures & Data

Figures

  • Tables
  • Additional Files
  • FIGURE 1.
    • Download figure
    • Open in new tab
    • Download powerpoint
    FIGURE 1.

    LuTate time–activity curve in blood up to 72 h after treatment. Each point represents single measurement of radioactivity in the blood of 11 patients at indicated times. Solid line is biexponential fit of LuTate disappearance from blood.

  • FIGURE 2.
    • Download figure
    • Open in new tab
    • Download powerpoint
    FIGURE 2.

    Kinetics of γ-H2AX foci formation in PBLs. (A) Representative confocal images of γ-H2AX foci (green) and nuclei (red, DNA) of patient P10.5 after administration of 8,362 MBq of LuTate. Values correspond to average number of foci per cell ± SEM. (B) Number of foci per cell in individual patients measured at baseline (BL) before therapy and 10, 20, and 30 min and at 1, 2, 4, 24, 48, and 72 h after LuTate administration in one or more cycles of therapy.

  • FIGURE 3.
    • Download figure
    • Open in new tab
    • Download powerpoint
    FIGURE 3.

    Analysis of γ-H2AX foci formation in PBLs. (A) Number of foci per cell vs. time after PRRT for individual patient. Black horizontal bar and error bars represent mean ± SEM of 14–16 samples. (B) Fraction of cells with no foci (blue bars), ≤3 foci (red bars), and ≥4 foci (green bars) (mean ± SEM, n = 14–16). (C) Simulation of number of foci per cell as function of time after PRRT. Symbols represent average experimental values across all patients ± SD. Simulation was implemented for radiation dose of 42 mGy delivered as pulse (blue line) or accumulated (red line) within 80-h interval. Accumulated dose was calculated according to LuTate kinetics in blood (black line). *P < 0.05, Mann–Whitney test, for baseline vs. other time points. **P < 0.01, Mann–Whitney test, for baseline vs. other time points.

  • FIGURE 4.
    • Download figure
    • Open in new tab
    • Download powerpoint
    FIGURE 4.

    Correlation studies. (A) Peak number of excess foci per cell in 10-min to 4-h interval vs. dose to blood at 2 h. (B) Peak number of excess foci per cell in 24- to 72-h interval vs. tumor dose. (C) Peak number of foci per cell in 10-min to 4-h interval vs. dose to bone marrow. (D) Peak number of excess foci per cell in 10-min to 4-h interval vs. lymphocyte reduction 2 wk after treatment. Data for different treatment cycles of same patient are shown as blue (P1), green (P2), and black (P3) symbols; other data points are shown as red symbols. Red lines represent linear regression for all points.

Tables

  • Figures
  • Additional Files
    • View popup
    TABLE 1

    Demographics and Characteristics of Patients

    Patient blood identifierSexAge at treatment (y)Body weight (kg)DiagnosisPrimary siteTreatments before PRRT5-FU in combination with PRRT
    P1.1M4698NeuroendocrinePancreasChemotherapy+
    P1.2M4796NeuroendocrinePancreasChemotherapy+
    P1.3M47100.4NeuroendocrinePancreasChemotherapy+
    P2.2M6282.3CarcinoidSmall bowelNil−
    P2.3M6282CarcinoidSmall bowelNil+
    P2.5M6280.1CarcinoidSmall bowelNil+
    P3.3F46133NeuroendocrineSmall bowelNil+
    P3.4F46130NeuroendocrineSmall bowelNil+
    P4.1M5577CarcinoidBowelSurgery−
    P5.1F5279NeuroendocrineSmall bowelChemotherapy/Sandostatin+
    P6.1M5781NeuroendocrinePancreasSandostatin−
    P7.3F4958.6Islet cellPancreasSurgery+
    P8.3M3285NeuroendocrinePancreasSurgery+
    P9.3F4677GlucagonomaPancreasChemotherapy/Sandostatin/surgery+
    P10.5F6583GastrinomaDuodenumChemotherapy+
    P11.6M60114CarcinoidUnknownChemotherapy/Sandostatin−
    • Patients are numbered from P1 to P11 followed by treatment cycle number. Sandostatin (Novartis AG Corp.) is a long-acting octreotide.

    • View popup
    TABLE 2

    Dosimetry

    Patient blood identifierOctreotate-avid tumor volume at treatment (cm3)Administered activity (MBq)Cumulative absorbed dose to blood at 72 h (mGy)Cumulative absorbed dose to blood at 2 h (mGy)Absorbed dose to spleen (mGy)Absorbed dose to bone marrow (mGy)Absorbed dose to tumor (mGy)*
    P1.16409,00040102,80021037,000
    P1.27007,0002273,60021031,000
    P1.37208,00033122,00020023,000
    P2.23,10010,00057163,20037030,000
    P2.33,3007,90052143,40041024,000
    P2.53,0007,800378NDNDND
    P3.34209,30055223,30027014,000
    P3.42406,50024111,70019013,000
    P4.1947,100NDNDNDNDND
    P5.11306,900NDND1,70025012,000
    P6.11,2007,700451110,00019046,000
    P7.3NDNDND17NDNDND
    P8.3298,600NDND6,1002006,000
    P9.3306,800NDND3,4002807,000
    P10.51108,40052215,10028020,000
    P11.69006,700NDND1,90017018,000
    • ↵* For multiple lesions, lesion with highest value was used.

    • ND = not determined.

    • Patients are numbered from P1 to P11 followed by treatment cycle number.

    • View popup
    TABLE 3

    Lymphocyte Toxicity After PRRT

    Patient blood identifierBaseline PBL count before first treatment (cells × 103/mm3)PBL counts before indicated treatment* (cells × 103/mm3)PBL count 2 wk after indicated treatment* (cells × 103/mm3)PBL reduction (%) before indicated treatment to 2 wk after indicated treatmentPBL reduction (%) between baseline and 2 wk after indicated treatment
    P1.11.61.60.66363
    P1.21.60.80.53869
    P1.31.61.00.55069
    P2.21.41.00.55064
    P2.31.40.50.42071
    P2.51.40.50.34079
    P3.32.91.80.95069
    P3.42.91.10.91869
    P4.11.21.20.83333
    P5.11.51.50.84747
    P6.12.32.30.96161
    P7.32.50.50.34088
    P8.31.70.90.63365
    P9.31.30.90.45670
    P10.51.91.20.65068
    P11.62.31.71.51234
    • ↵* “Indicated treatment” refers to treatment cycle number denoted by last digit in patient blood identifier.

    • Patients are numbered from P1 to P11 followed by treatment cycle number.

Additional Files

  • Figures
  • Tables
  • Supplemental Data

    Files in this Data Supplement:

    • Supplemental Data
PreviousNext
Back to top

In this issue

Journal of Nuclear Medicine: 56 (4)
Journal of Nuclear Medicine
Vol. 56, Issue 4
April 1, 2015
  • 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.
Analysis of 177Lu-DOTA-Octreotate Therapy–Induced DNA Damage in Peripheral Blood Lymphocytes of Patients with Neuroendocrine Tumors
(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
Analysis of 177Lu-DOTA-Octreotate Therapy–Induced DNA Damage in Peripheral Blood Lymphocytes of Patients with Neuroendocrine Tumors
Delphine Denoyer, Pavel Lobachevsky, Price Jackson, Mick Thompson, Olga A. Martin, Rodney J. Hicks
Journal of Nuclear Medicine Apr 2015, 56 (4) 505-511; DOI: 10.2967/jnumed.114.145581

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
Analysis of 177Lu-DOTA-Octreotate Therapy–Induced DNA Damage in Peripheral Blood Lymphocytes of Patients with Neuroendocrine Tumors
Delphine Denoyer, Pavel Lobachevsky, Price Jackson, Mick Thompson, Olga A. Martin, Rodney J. Hicks
Journal of Nuclear Medicine Apr 2015, 56 (4) 505-511; DOI: 10.2967/jnumed.114.145581
Twitter logo Facebook logo LinkedIn logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One
Bookmark this article

Jump to section

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

Related Articles

  • γ-H2AX Foci in Peripheral Blood Lymphocytes to Quantify Radiation-Induced DNA Damage After 177Lu-DOTA-Octreotate Peptide Receptor Radionuclide Therapy
  • This Month in JNM
  • PubMed
  • Google Scholar

Cited By...

  • Dosimetric Evaluation of the Effect of Receptor Heterogeneity on the Therapeutic Efficacy of Peptide Receptor Radionuclide Therapy: Correlation with DNA Damage Induction and In Vivo Survival
  • Dissimilar DNA Damage to Blood Lymphocytes After 177Lu-Labeled DOTATOC or Prostate-Specific Membrane Antigen Therapy
  • Peptide Receptor Radionuclide Therapy During the COVID-19 Pandemic: Are There Any Concerns?
  • Imaging DNA Damage Repair In Vivo After 177Lu-DOTATATE Therapy
  • Identification of brain metastasis genes and therapeutic evaluation of histone deacetylase inhibitors in a clinically relevant model of breast cancer brain metastasis
  • The Relevance of Dosimetry in Precision Medicine
  • Identification of brain metastasis genes and therapeutic evaluation of histone deacetylase inhibitors in a clinically relevant model of breast cancer brain metastasis
  • Localized Synchrotron Irradiation of Mouse Skin Induces Persistent Systemic Genotoxic and Immune Responses
  • Radiotherapy for Non-Small Cell Lung Cancer Induces DNA Damage Response in Both Irradiated and Out-of-field Normal Tissues
  • Myeloid neoplasms after chemotherapy and PRRT: myth and reality
  • DNA Damage in Peripheral Blood Lymphocytes of Thyroid Cancer Patients After Radioiodine Therapy
  • Radiopeptides for Imaging and Therapy: A Radiant Future
  • {gamma}-H2AX Foci in Peripheral Blood Lymphocytes to Quantify Radiation-Induced DNA Damage After 177Lu-DOTA-Octreotate Peptide Receptor Radionuclide Therapy
  • Google Scholar

More in this TOC Section

  • Feasibility of Ultra-Low-Activity 18F-FDG PET/CT Imaging Using a Long–Axial-Field-of-View PET/CT System
  • Cardiac Presynaptic Sympathetic Nervous Function Evaluated by Cardiac PET in Patients with Chronotropic Incompetence Without Heart Failure
  • Validation and Evaluation of a Vendor-Provided Head Motion Correction Algorithm on the uMI Panorama PET/CT System
Show more Clinical Investigations

Similar Articles

Keywords

  • 177Lu-octreotate
  • PRRT
  • normal tissue toxicity
  • DNA damage
  • γ-H2AX
SNMMI

© 2025 SNMMI

Powered by HighWire