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Preliminary results of the Phase 1 Lip-Re I clinical trial: biodistribution and dosimetry assessments in hepatocellular carcinoma patients treated with 188Re-SSS Lipiodol radioembolization

  • Kostas Delaunay
  • Julien Edeline
  • Yan Rolland
  • Nicolas Lepareur
  • Sophie Laffont
  • Xavier Palard
  • Christelle Bouvry
  • Samuel Le Sourd
  • Marc Pracht
  • Valérie Ardisson
  • Nicolas Noiret
  • Éric Bellissant
  • Etienne GarinEmail author
Original Article

Abstract

Purpose

This study sought to provide preliminary results on the biodistribution and dosimetry following intra-arterial liver injection of 188Re-SSS Lipiodol on hepatocellular carcinoma patients included in the Phase I Lip-Re 1 study.

Methods

Results of the first six patients included are reported. Analysis of the 188Re-SSS Lipiodol biodistribution was based on planar scintigraphic and tomoscintigraphic (SPECT) studies performed at 1, 6, 24, 48, and 72 h post-administration. Quantification in blood, urine, and stool samples was performed. Determination of the tumour to non-tumour uptake ratio (T/NT) was calculated. Absorbed doses to target organs and tumours were evaluated using the MIRD formalism.

Results

The mean injected activity of 188Re-SSS Lipiodol was 1645 ± 361 MBq. Uptakes were seen in the liver (tumour and healthy liver) and the lungs only. All these uptakes were stable over time. A mean 1.4 ± 0.7% of 188Re-SSS Lipiodol administered was detected in serum samples at 6 h, declining rapidly thereafter. On average, 1.5 ± 1.6% of administered activity was eliminated in urine and feces over 72 h. Overall, 90.7 ± 1.6% of detected activity on SPECT studies was found in the liver (74.9 ± 1.8% in tumours and 19.1 ± 1.7% in the healthy liver) and 9.3 ± 1.6% in the lungs (5.7 ± 1.1% in right and 3.7 ± 0.5% in left lungs). Mean doses absorbed were 7.9 ± 3.7Gy to the whole liver, 42.7 ± 34.0Gy to the tumours, 10.2 ± 3.7Gy to the healthy liver, and 1.5 ± 1.2Gy to the lungs. Four patients had stable disease on CT scans at 2 months. The first patient with rapidly progressive disease died at 1 month, most probably of massive tumour progression. Due to this early death and using a conservative approach, the trial independent evaluation committee decided to consider this event as a treatment-related toxicity.

Conclusion

188Re-SSS Lipiodol has a favorable biodistribution profile concerning radioembolization, with the highest in-vivo stability among all radiolabeled Lipiodol compounds reported to date. These preliminary results must be further confirmed while completing this Phase I Lip Re1 study.

Keywords

188Re Lipiodol Hepatocellular carcinoma Liver Oncology 

Notes

Acknowledgements

This work has been supported in part by a grant from the French National Agency for Research called “Investissements d’Avenir” Labex IRON n°ANR-11-LABX-0018-01.

We are grateful to Prof Mario Marengo, from Bologna University, for his help with the calibration settings for 188Re.

Compliance with ethical standards

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Conflict of interest

Yan Rolland, Julien Edeline, and Etienne Garin are consultants for BTG UK Ltd.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Kostas Delaunay
    • 1
    • 2
  • Julien Edeline
    • 2
    • 3
    • 4
  • Yan Rolland
    • 5
    • 6
  • Nicolas Lepareur
    • 4
    • 7
  • Sophie Laffont
    • 1
  • Xavier Palard
    • 1
    • 2
  • Christelle Bouvry
    • 7
  • Samuel Le Sourd
    • 3
  • Marc Pracht
    • 3
  • Valérie Ardisson
    • 7
  • Nicolas Noiret
    • 8
  • Éric Bellissant
    • 2
    • 9
    • 10
  • Etienne Garin
    • 1
    • 2
    • 4
    Email author
  1. 1.Department of Nuclear MedicineCancer Institute Eugène MarquisRennesFrance
  2. 2.University of Rennes 1RennesFrance
  3. 3.Department of Medical OncologyCancer Institute Eugène MarquisRennesFrance
  4. 4.INSERM INRA UMR 1241 NuMeCanUniversity of Rennes 1RennesFrance
  5. 5.Department of Medical ImagingCancer Institute Eugène MarquisRennesFrance
  6. 6.INSERM UMR 1099 LTSIUniversity of Rennes 1RennesFrance
  7. 7.RadiopharmacyCancer Institute Eugène MarquisRennesFrance
  8. 8.ENSCR, CNRS, ISCR [(Institut des Sciences Chimiques de Rennes)] - UMR 6226University of RennesRennesFrance
  9. 9.INSERM CIC 1414 Clinical Investigation CenterRennesFrance
  10. 10.Department of Clinical and Biological Pharmacology and Pharmacovigilance, Pharmaco-epidemiology and Drug Information CenterRennes University HospitalRennesFrance

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