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

doi:10.1016/j.nucmedbio.2019.03.001

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 journal › Article › Academic › peer-review

Abstract

BACKGROUND: [166Ho]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 [166Ho]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 [166Ho]Ho3+ pre-administration using phosphate. The in vitro near-maximum neutron irradiation experiments showed significant [166Ho]Ho-AcAc-PLLA microsphere damage.

CONCLUSION: The amount of holmium in the peripheral blood and urine samples after [166Ho]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 language	English
Pages (from-to)	11-18
Number of pages	8
Journal	Nuclear medicine and biology
Volume	71
DOIs	https://doi.org/10.1016/j.nucmedbio.2019.03.001
Publication status	Published - 1 Apr 2019

Keywords

SIRT
Holmium
Radioisotope
Blood
Urine

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@article{8e207a3c7f4a4ef696045b9fdefabecb,

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

abstract = "BACKGROUND: [166Ho]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 [166Ho]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 [166Ho]Ho3+ pre-administration using phosphate. The in vitro near-maximum neutron irradiation experiments showed significant [166Ho]Ho-AcAc-PLLA microsphere damage.CONCLUSION: The amount of holmium in the peripheral blood and urine samples after [166Ho]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 = "SIRT, Holmium, Radioisotope, Blood, Urine",

author = "Bakker, {Robbert C} and {de Roos}, Remmert and Ververs, {F F Tessa} and Lam, {Marnix G E H} and {van der Lee}, {Martijn K} and Zonnenberg, {Bernard A} and Krijger, {Gerard C}",

note = "Funding Information: R.C. Bakker is funded by the Dutch Cancer Society research grant: 2014-7075 . Funding Information: The department of Radiology and Nuclear Medicine of the UMC Utrecht receives royalties and research funding from Quirem Medical B.V. and Terumo. Funding Information: The authors would like to acknowledge Dr. J.F.W. Nijsen and Dr. A.D. van het Schip for their contributions in product management and study designs, and G. van Bemmel and B. Aolad-si Mhammad for their help with analyses and data management. R.C. Bakker is funded by the Dutch Cancer Society research grant: 2014-7075. Funding Information: B.A. Zonnenberg holds patents related to holmium microspheres, which are assigned to University Medical Center Utrecht Holding BV. He receives honoraria from GSK Netherlands and consulted for, received research funding from and had expenses reimbursed by Novartis pharm Inc. Publisher Copyright: {\textcopyright} 2019 The Authors",

year = "2019",

month = apr,

day = "1",

doi = "10.1016/j.nucmedbio.2019.03.001",

language = "English",

volume = "71",

pages = "11--18",

journal = "Nuclear medicine and biology",

issn = "0969-8051",

publisher = "Elsevier",

}

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 - Ververs, F F Tessa

AU - Lam, Marnix G E H

AU - van der Lee, Martijn K

AU - Zonnenberg, Bernard A

AU - Krijger, Gerard C

N1 - Funding Information: R.C. Bakker is funded by the Dutch Cancer Society research grant: 2014-7075 . Funding Information: The department of Radiology and Nuclear Medicine of the UMC Utrecht receives royalties and research funding from Quirem Medical B.V. and Terumo. Funding Information: The authors would like to acknowledge Dr. J.F.W. Nijsen and Dr. A.D. van het Schip for their contributions in product management and study designs, and G. van Bemmel and B. Aolad-si Mhammad for their help with analyses and data management. R.C. Bakker is funded by the Dutch Cancer Society research grant: 2014-7075. Funding Information: B.A. Zonnenberg holds patents related to holmium microspheres, which are assigned to University Medical Center Utrecht Holding BV. He receives honoraria from GSK Netherlands and consulted for, received research funding from and had expenses reimbursed by Novartis pharm Inc. Publisher Copyright: © 2019 The Authors

PY - 2019/4/1

Y1 - 2019/4/1

N2 - BACKGROUND: [166Ho]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 [166Ho]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 [166Ho]Ho3+ pre-administration using phosphate. The in vitro near-maximum neutron irradiation experiments showed significant [166Ho]Ho-AcAc-PLLA microsphere damage.CONCLUSION: The amount of holmium in the peripheral blood and urine samples after [166Ho]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: [166Ho]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 [166Ho]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 [166Ho]Ho3+ pre-administration using phosphate. The in vitro near-maximum neutron irradiation experiments showed significant [166Ho]Ho-AcAc-PLLA microsphere damage.CONCLUSION: The amount of holmium in the peripheral blood and urine samples after [166Ho]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 - SIRT

KW - Holmium

KW - Radioisotope

KW - Blood

KW - Urine

UR - http://www.scopus.com/inward/record.url?scp=85065719004&partnerID=8YFLogxK

U2 - 10.1016/j.nucmedbio.2019.03.001

DO - 10.1016/j.nucmedbio.2019.03.001

M3 - Article

C2 - 31108463

SN - 0969-8051

VL - 71

SP - 11

EP - 18

JO - Nuclear medicine and biology

JF - Nuclear medicine and biology

ER -

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

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Keywords

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