Preparation and characterization of inorganic radioactive holmium-166 microspheres for internal radionuclide therapy

A. G. Arranja; W. E. Hennink; C. Chassagne; A. G. Denkova; J. F.W. Nijsen

doi:10.1016/j.msec.2019.110244

Preparation and characterization of inorganic radioactive holmium-166 microspheres for internal radionuclide therapy

A. G. Arranja, W. E. Hennink, C. Chassagne, A. G. Denkova, J. F.W. Nijsen^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Scientific › peer-review

9 Citations (Scopus)

Abstract

Microspheres with high specific activities of radionuclides are very interesting for internal radiotherapy treatments. This work focuses on the formulation and characterization of inorganic microspheres with a high content of holmium and therefore a high specific radioactivity of holmium-166. Two novel formulations of inorganic microspheres were obtained by dispersing solid holmium acetylacetonate microspheres (Ho₂(AcAc)₃-ms) in NaH₂PO₄ or NaOH solutions followed by 2 h incubation at room temperature. By exchange of acetylacetonate with phosphate or hydroxyl ions, holmium phosphate microspheres (HoPO₄-ms) and holmium hydroxide microspheres (Ho(OH)₃-ms) were formed respectively. The inorganic microspheres had a significantly smaller diameter (28.5 ± 4.4 μm (HoPO₄-ms) and 25.1 ± 3.5 μm (Ho(OH)₃-ms)) than those of Ho₂(AcAc)₃-ms (32.6 ± 5.2 μm). The weight percentage of holmium-165 in the microspheres increased significantly from 47% (Ho₂(AcAc)₃-ms) to 55% (HoPO₄-ms) and 73% (Ho(OH)₃-ms). After preparation of both HoPO₄-ms and Ho(OH)₃-ms, the stable holmium-165 isotope was partly converted by neutron activation into radioactive holmium-166 to yield radioactive microspheres. High specific activities were achieved ranging from 21.7 to 59.9 MBq/mg (¹⁶⁶HoPO₄-ms) and from 28.8 to 79.9 MBq/mg (¹⁶⁶Ho(OH)₃-ms) depending on the neutron activation time. The structure of both microspheres was preserved up to neutron activations of 6 h in a thermal neutron flux of 4.72 × 10¹⁶ n m⁻² s⁻¹. After activation, both microspheres revealed excellent stability in administration fluids (saline and phosphate buffer) having less than 0.05% of holmium released after 72 h incubation. Finally, the hemocompatibility of these inorganic microspheres was evaluated and it was shown that the microspheres did cause neither hemolysis nor depletion or inhibition of the coagulation factors of the intrinsic blood coagulation pathway meaning that the microspheres have a good hemocompatibility. Overall, this work shows that radioactive inorganic microspheres with high specific activities of holmium-166 can be prepared which potentially can be used for internal radionuclide therapy.

Original language	English
Article number	110244
Number of pages	11
Journal	Materials Science and Engineering C
Volume	106
DOIs	https://doi.org/10.1016/j.msec.2019.110244
Publication status	Published - 2020

Keywords

Hemocompatibility
Holmium hydroxide
Holmium phosphate
Microspheres
Neutron activation
Radionuclide therapy

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10.1016/j.msec.2019.110244

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@article{c48072f7505148de890ba4857effea52,

title = "Preparation and characterization of inorganic radioactive holmium-166 microspheres for internal radionuclide therapy",

abstract = "Microspheres with high specific activities of radionuclides are very interesting for internal radiotherapy treatments. This work focuses on the formulation and characterization of inorganic microspheres with a high content of holmium and therefore a high specific radioactivity of holmium-166. Two novel formulations of inorganic microspheres were obtained by dispersing solid holmium acetylacetonate microspheres (Ho2(AcAc)3-ms) in NaH2PO4 or NaOH solutions followed by 2 h incubation at room temperature. By exchange of acetylacetonate with phosphate or hydroxyl ions, holmium phosphate microspheres (HoPO4-ms) and holmium hydroxide microspheres (Ho(OH)3-ms) were formed respectively. The inorganic microspheres had a significantly smaller diameter (28.5 ± 4.4 μm (HoPO4-ms) and 25.1 ± 3.5 μm (Ho(OH)3-ms)) than those of Ho2(AcAc)3-ms (32.6 ± 5.2 μm). The weight percentage of holmium-165 in the microspheres increased significantly from 47% (Ho2(AcAc)3-ms) to 55% (HoPO4-ms) and 73% (Ho(OH)3-ms). After preparation of both HoPO4-ms and Ho(OH)3-ms, the stable holmium-165 isotope was partly converted by neutron activation into radioactive holmium-166 to yield radioactive microspheres. High specific activities were achieved ranging from 21.7 to 59.9 MBq/mg (166HoPO4-ms) and from 28.8 to 79.9 MBq/mg (166Ho(OH)3-ms) depending on the neutron activation time. The structure of both microspheres was preserved up to neutron activations of 6 h in a thermal neutron flux of 4.72 × 1016 n m−2 s−1. After activation, both microspheres revealed excellent stability in administration fluids (saline and phosphate buffer) having less than 0.05% of holmium released after 72 h incubation. Finally, the hemocompatibility of these inorganic microspheres was evaluated and it was shown that the microspheres did cause neither hemolysis nor depletion or inhibition of the coagulation factors of the intrinsic blood coagulation pathway meaning that the microspheres have a good hemocompatibility. Overall, this work shows that radioactive inorganic microspheres with high specific activities of holmium-166 can be prepared which potentially can be used for internal radionuclide therapy.",

keywords = "Hemocompatibility, Holmium hydroxide, Holmium phosphate, Microspheres, Neutron activation, Radionuclide therapy",

author = "Arranja, {A. G.} and Hennink, {W. E.} and C. Chassagne and Denkova, {A. G.} and Nijsen, {J. F.W.}",

year = "2020",

doi = "10.1016/j.msec.2019.110244",

language = "English",

volume = "106",

journal = "Materials Science and Engineering C",

issn = "0928-4931",

publisher = "Elsevier",

}

TY - JOUR

T1 - Preparation and characterization of inorganic radioactive holmium-166 microspheres for internal radionuclide therapy

AU - Arranja, A. G.

AU - Hennink, W. E.

AU - Chassagne, C.

AU - Denkova, A. G.

AU - Nijsen, J. F.W.

PY - 2020

Y1 - 2020

N2 - Microspheres with high specific activities of radionuclides are very interesting for internal radiotherapy treatments. This work focuses on the formulation and characterization of inorganic microspheres with a high content of holmium and therefore a high specific radioactivity of holmium-166. Two novel formulations of inorganic microspheres were obtained by dispersing solid holmium acetylacetonate microspheres (Ho2(AcAc)3-ms) in NaH2PO4 or NaOH solutions followed by 2 h incubation at room temperature. By exchange of acetylacetonate with phosphate or hydroxyl ions, holmium phosphate microspheres (HoPO4-ms) and holmium hydroxide microspheres (Ho(OH)3-ms) were formed respectively. The inorganic microspheres had a significantly smaller diameter (28.5 ± 4.4 μm (HoPO4-ms) and 25.1 ± 3.5 μm (Ho(OH)3-ms)) than those of Ho2(AcAc)3-ms (32.6 ± 5.2 μm). The weight percentage of holmium-165 in the microspheres increased significantly from 47% (Ho2(AcAc)3-ms) to 55% (HoPO4-ms) and 73% (Ho(OH)3-ms). After preparation of both HoPO4-ms and Ho(OH)3-ms, the stable holmium-165 isotope was partly converted by neutron activation into radioactive holmium-166 to yield radioactive microspheres. High specific activities were achieved ranging from 21.7 to 59.9 MBq/mg (166HoPO4-ms) and from 28.8 to 79.9 MBq/mg (166Ho(OH)3-ms) depending on the neutron activation time. The structure of both microspheres was preserved up to neutron activations of 6 h in a thermal neutron flux of 4.72 × 1016 n m−2 s−1. After activation, both microspheres revealed excellent stability in administration fluids (saline and phosphate buffer) having less than 0.05% of holmium released after 72 h incubation. Finally, the hemocompatibility of these inorganic microspheres was evaluated and it was shown that the microspheres did cause neither hemolysis nor depletion or inhibition of the coagulation factors of the intrinsic blood coagulation pathway meaning that the microspheres have a good hemocompatibility. Overall, this work shows that radioactive inorganic microspheres with high specific activities of holmium-166 can be prepared which potentially can be used for internal radionuclide therapy.

AB - Microspheres with high specific activities of radionuclides are very interesting for internal radiotherapy treatments. This work focuses on the formulation and characterization of inorganic microspheres with a high content of holmium and therefore a high specific radioactivity of holmium-166. Two novel formulations of inorganic microspheres were obtained by dispersing solid holmium acetylacetonate microspheres (Ho2(AcAc)3-ms) in NaH2PO4 or NaOH solutions followed by 2 h incubation at room temperature. By exchange of acetylacetonate with phosphate or hydroxyl ions, holmium phosphate microspheres (HoPO4-ms) and holmium hydroxide microspheres (Ho(OH)3-ms) were formed respectively. The inorganic microspheres had a significantly smaller diameter (28.5 ± 4.4 μm (HoPO4-ms) and 25.1 ± 3.5 μm (Ho(OH)3-ms)) than those of Ho2(AcAc)3-ms (32.6 ± 5.2 μm). The weight percentage of holmium-165 in the microspheres increased significantly from 47% (Ho2(AcAc)3-ms) to 55% (HoPO4-ms) and 73% (Ho(OH)3-ms). After preparation of both HoPO4-ms and Ho(OH)3-ms, the stable holmium-165 isotope was partly converted by neutron activation into radioactive holmium-166 to yield radioactive microspheres. High specific activities were achieved ranging from 21.7 to 59.9 MBq/mg (166HoPO4-ms) and from 28.8 to 79.9 MBq/mg (166Ho(OH)3-ms) depending on the neutron activation time. The structure of both microspheres was preserved up to neutron activations of 6 h in a thermal neutron flux of 4.72 × 1016 n m−2 s−1. After activation, both microspheres revealed excellent stability in administration fluids (saline and phosphate buffer) having less than 0.05% of holmium released after 72 h incubation. Finally, the hemocompatibility of these inorganic microspheres was evaluated and it was shown that the microspheres did cause neither hemolysis nor depletion or inhibition of the coagulation factors of the intrinsic blood coagulation pathway meaning that the microspheres have a good hemocompatibility. Overall, this work shows that radioactive inorganic microspheres with high specific activities of holmium-166 can be prepared which potentially can be used for internal radionuclide therapy.

KW - Hemocompatibility

KW - Holmium hydroxide

KW - Holmium phosphate

KW - Microspheres

KW - Neutron activation

KW - Radionuclide therapy

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DO - 10.1016/j.msec.2019.110244

M3 - Article

C2 - 31753348

SN - 0928-4931

VL - 106

JO - Materials Science and Engineering C

JF - Materials Science and Engineering C

M1 - 110244

ER -

Preparation and characterization of inorganic radioactive holmium-166 microspheres for internal radionuclide therapy

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Keywords

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