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18.11.2019 | Original Article

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

Zeitschrift:
European Journal of Nuclear Medicine and Molecular Imaging
Autoren:
Alexander S. Pasciak, Godwin Abiola, Robert P. Liddell, Nathan Crookston, Sepideh Besharati, Danielle Donahue, Richard E. Thompson, Eric Frey, Robert A. Anders, Matthew R. Dreher, Clifford R. Weiss
Wichtige Hinweise

Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1007/​s00259-019-04588-x) contains supplementary material, which is available to authorized users.
This article is part of the Topical Collection on Oncology – Digestive tract.

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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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