|Title||Blood and urine analyses after radioembolization of liver malignancies with [166Ho]Ho-acetylacetonate-poly(L-lactic acid) microspheres|
|Author(s)||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.|
|Source||Nuclear medicine and biology 71 (2019). - ISSN 0969-8051 - p. 11 - 18.|
|Department(s)||BU Contaminants & Toxins|
|Publication type||Refereed Article in a scientific journal|
|Keyword(s)||Blood - Holmium - Radioisotope - SIRT - Urine|
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.