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

Research output: Contribution to journalArticleAcademicpeer-review

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.

LanguageEnglish
Pages11-18
Number of pages8
JournalNuclear medicine and biology
Volume71
DOIs
Publication statusPublished - 1 Apr 2019

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Microspheres
Urine
Holmium
Liver
Neutrons
Neoplasms
Hepatic Artery
Gamma Rays
Microscopy
Mass Spectrometry
Spectrum Analysis
Phosphates
High Pressure Liquid Chromatography
poly(lactic acid)
acetyl acetonate
Light
In Vitro Techniques
Clinical Studies

Keywords

  • Blood
  • Holmium
  • Radioisotope
  • SIRT
  • Urine

Cite this

Bakker, Robbert C. ; de Roos, Remmert ; Tessa Ververs, F.F. ; Lam, Marnix G.E.H. ; van der Lee, Martijn K. ; Zonnenberg, Bernard A. ; Krijger, Gerard C. / Blood and urine analyses after radioembolization of liver malignancies with [166Ho]Ho-acetylacetonate-poly(L-lactic acid) microspheres. In: Nuclear medicine and biology. 2019 ; Vol. 71. pp. 11-18.
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title = "Blood and urine analyses after radioembolization of liver malignancies with [166Ho]Ho-acetylacetonate-poly(L-lactic acid) microspheres",
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.",
keywords = "Blood, Holmium, Radioisotope, SIRT, Urine",
author = "Bakker, {Robbert C.} and {de Roos}, Remmert and {Tessa Ververs}, F.F. and Lam, {Marnix G.E.H.} and {van der Lee}, {Martijn K.} and Zonnenberg, {Bernard A.} and Krijger, {Gerard C.}",
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language = "English",
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Blood and urine analyses after radioembolization of liver malignancies with [166Ho]Ho-acetylacetonate-poly(L-lactic acid) microspheres. / Bakker, Robbert C.; de Roos, Remmert; Tessa Ververs, F.F.; Lam, Marnix G.E.H.; van der Lee, Martijn K.; Zonnenberg, Bernard A.; Krijger, Gerard C.

In: Nuclear medicine and biology, Vol. 71, 01.04.2019, p. 11-18.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Blood and urine analyses after radioembolization of liver malignancies with [166Ho]Ho-acetylacetonate-poly(L-lactic acid) microspheres

AU - Bakker, Robbert C.

AU - de Roos, Remmert

AU - Tessa Ververs, F.F.

AU - Lam, Marnix G.E.H.

AU - van der Lee, Martijn K.

AU - Zonnenberg, Bernard A.

AU - Krijger, Gerard C.

PY - 2019/4/1

Y1 - 2019/4/1

N2 - 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.

AB - 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.

KW - Blood

KW - Holmium

KW - Radioisotope

KW - SIRT

KW - Urine

U2 - 10.1016/j.nucmedbio.2019.03.001

DO - 10.1016/j.nucmedbio.2019.03.001

M3 - Article

VL - 71

SP - 11

EP - 18

JO - Nuclear medicine and biology

T2 - Nuclear medicine and biology

JF - Nuclear medicine and biology

SN - 0969-8051

ER -