1. Blood and urine analyses after radioembolization of liver malignancies with [166Ho]Ho-acetylacetonate-poly(L-lactic acid) microspheres
- Author
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Bakker, Robbert C., Roos, Remmert, de, Tessa Ververs, F.F., Lam, Marnix G.E.H., Lee, Martijn K., van der, Zonnenberg, Bernard A., Krijger, Gerard C., Bakker, Robbert C., Roos, Remmert, de, Tessa Ververs, F.F., Lam, Marnix G.E.H., Lee, Martijn K., van der, Zonnenberg, Bernard A., and Krijger, Gerard C.
- 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.
- Published
- 2019