Blood and urine analyses after radioembolization of liver malignancies with [166Ho]Ho-acetylacetonate-poly(L-lactic acid) microspheres

Robbert C. Bakker, Remmert de Roos, F.F. Tessa Ververs, Marnix G.E.H. Lam, Martijn K. van der Lee, Bernard A. Zonnenberg, Gerard C. Krijger*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Background: [ 166 Ho]Ho-acetylacetonate-poly(L-lactic acid) microspheres were used in radioembolization of liver malignancies by intra-arterial administration. The primary aim of this study was to assess the stability and biodistribution of these microspheres. Materials and methods: Peripheral blood and urine samples were obtained from two clinical studies. Patient and in vitro experiment samples were analyzed using inductively coupled plasma mass spectrometry (ICP-MS), gamma-ray spectroscopy, light microscopy, Coulter particle counting, and high performance liquid chromatography (HPLC). Results: The median percentage holmium compared to the total amount injected into the hepatic artery was 0.19% (range 0.08–2.8%) and 0.32% (range 0.03–1.8%) in the 1 h blood plasma and 24 h urine, respectively. Both the blood plasma and urine were correlated with the neutron irradiation exposure required for [ 166 Ho]Ho-AcAc-PLLA microsphere production (ρ = 0.616, p = 0.002). After a temporary interruption of the phase 2 clinical study, the resuspension medium was replaced to precipitate [ 166 Ho]Ho 3+ pre-administration using phosphate. The in vitro near-maximum neutron irradiation experiments showed significant [ 166 Ho]Ho-AcAc-PLLA microsphere damage. Conclusion: The amount of holmium in the peripheral blood and urine samples after [ 166 Ho]Ho-AcAc-PLLA microsphere intrahepatic infusion was low. A further decrease was observed after reformulation of the resuspension solution but minimization of production damage is necessary.

Original languageEnglish
Pages (from-to)11-18
Number of pages8
JournalNuclear medicine and biology
Volume71
DOIs
Publication statusPublished - 1 Apr 2019

Keywords

  • Blood
  • Holmium
  • Radioisotope
  • SIRT
  • Urine

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    Bakker, R. C., de Roos, R., Tessa Ververs, F. F., Lam, M. G. E. H., van der Lee, M. K., Zonnenberg, B. A., & Krijger, G. C. (2019). Blood and urine analyses after radioembolization of liver malignancies with [166Ho]Ho-acetylacetonate-poly(L-lactic acid) microspheres. Nuclear medicine and biology, 71, 11-18. https://doi.org/10.1016/j.nucmedbio.2019.03.001