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The number of microspheres in Y90 radioembolization directly affects normal tissue radiation exposure

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

In Y90 radioembolization, the number of microspheres infused varies by more than a factor of 20 over the shelf-life of the glass radioembolization device. We investigated the effect of the number of Y90 microspheres on normal liver tissue.

Method

Healthy pigs received lobar radioembolization with glass Y90 microspheres at 4, 8, 12, and 16 days post-calibration, representing a > 20× range in the number of microspheres deposited per milliliter in tissue. Animals were survived for 1-month post-treatment and the livers were explanted and scanned on a micro CT system to fully characterize the microscopic distribution of individual microspheres. A complete 3D microdosimetric evaluation of each liver was performed with a spatially correlated analysis of histopathologic effect.

Results

Through whole-lobe microscopic identification of each microsphere, a consistent number of microspheres per sphere cluster was found at 4, 8, and 12 days postcalibration, despite an 8-fold increase in total microspheres infused from days 4 to 12. The additional microspheres instead resulted in more clusters formed and, therefore, a more homogeneous microscopic absorbed dose. The increased absorbed-dose homogeneity resulted in a greater volume fraction of the liver receiving a potentially toxic absorbed dose based on radiobiologic models. Histopathologic findings in the animals support a possible increase in normal liver toxicity in later treatments with more spheres (i.e., ≥ day 12) compared to early treatments with less spheres (i.e., ≤ day 8).

Conclusion

The microdosimetric evidence presented supports a recommendation of caution when treating large volumes (e.g., right lobe) using glass 90Y microspheres at more than 8 days post-calibration, i.e., after “2nd week” Monday. The favorable normal tissue microscopic distribution and associated low toxicity of first week therapies may encourage opportunities for dose escalation with glass microspheres and could also be considered for patients with decreased hepatic reserve.

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Abbreviations

TARE:

Trans-arterial radioembolization

SA:

Specific activity

NL:

Normal liver

90Y:

Yttrium-90

MS/mL:

microspheres per milliliter

DPK:

Dose-point kernel

DVH:

Dose-volume histogram

V20:

The percent volume of tissue receiving more than 20Gy

CPE:

Charged particle equilibrium

NTCP:

Normal tissue complication probability

H&E:

Hematoxylin-eosin

CVC:

Central-vein changes

MIRD:

Medical internal radiation dose

T:N:

Tumor to normal uptake ratio

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Acknowledgments

This project was supported by a grant from Biocompatibles UK Ltd, a BTG International group company. The investigators wish to acknowledge the contribution of Robert S. Balaban, Ph.D., and the National Heart, Lung and Blood Institute at the National Institute of Health for supplying the Micro CT system used in this study. We also wish to acknowledge input from Riad Salem, MD, in the writing of this manuscript.

Funding

This study was funded by Biocompatables, PLC

Author information

Authors and Affiliations

  1. School of Medicine, The Johns Hopkins Hospital, 733 N Broadway, Baltimore, MD, 21205, USA

    Alexander S. Pasciak & Godwin Abiola

  2. Department of Radiology, Division of Vascular and Interventional Radiology, The Johns Hopkins Hospital, Baltimore, MD, USA

    Robert P. Liddell & Clifford R. Weiss

  3. Department of Electrical Engineering, The Johns Hopkins University, Baltimore, MD, USA

    Nathan Crookston

  4. Department of Pathology, The Johns Hopkins University, Baltimore, MD, USA

    Sepideh Besharati & Robert A. Anders

  5. Mouse Imaging Facility, National Institutes of Health, Bethesda, MD, USA

    Danielle Donahue

  6. Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA

    Richard E. Thompson

  7. Radiological Physics Division, Russell H Morgan Department of Radiology and Radiological Science, The Johns Hopkins Hospital, Baltimore, MD, USA

    Eric Frey

  8. Biocompatibles UK Ltd, BTG International group company, Farnham, Surrey, UK

    Matthew R. Dreher

Authors
  1. Alexander S. Pasciak
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Corresponding author

Correspondence to Alexander S. Pasciak.

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Conflict of interest

Author ASP, RPL, and CRW have received research grants from Biocompatables PLC. MRD is an employee of Biocompatables PLC. The remaining authors declare no conflict of interest.

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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. This article does not contain any studies with human participants performed by any of the authors.

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Pasciak, A.S., Abiola, G., Liddell, R.P. et al. The number of microspheres in Y90 radioembolization directly affects normal tissue radiation exposure. Eur J Nucl Med Mol Imaging 47, 816–827 (2020). https://doi.org/10.1007/s00259-019-04588-x

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  • DOI: https://doi.org/10.1007/s00259-019-04588-x

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