Author(s) Bakker, R.C.; de Roos, R.; Ververs, F.F.Tessa; Lam, M.G.E.H.; van der Lee, M.K.; Zonnenberg, B.A.; Krijger, G.C.
Journal Nucl Med Biol
Date Published 2019 Apr
Abstract

BACKGROUND: [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 [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 [Ho]Ho pre-administration using phosphate. The in vitro near-maximum neutron irradiation experiments showed significant [Ho]Ho-AcAc-PLLA microsphere damage.

CONCLUSION: The amount of holmium in the peripheral blood and urine samples after [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.

DOI 10.1016/j.nucmedbio.2019.03.001
ISSN 1872-9614
Citation Nucl Med Biol. 2019;71:1118.

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