Radiolabeling of human serum albumin with terbium-161 using mild conditions and evaluation of in vivo Stability

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Radiolabeling of human serum albumin with terbium-161 using mild conditions and evaluation of in vivo Stability. / Cassells, Irwin; Ahenkorah, Stephen; Burgoyne, Andrew; Van de Voorde, Michiel; Deroose, Christophe; Cardinaels, Thomas; Bormans, Guy; Ooms, Maarten; Cleeren, Frederik.

In: Frontiers in Medicine, Vol. 8, 675122, 18.08.2021, p. 1-12.

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@article{b13c9ccc35764321a0c0a91cf1e6c43b,
title = "Radiolabeling of human serum albumin with terbium-161 using mild conditions and evaluation of in vivo Stability",
abstract = "Targeted radionuclide therapy (TRNT) is a promising approach for cancer therapy. Terbium has four medically interesting isotopes (149Tb, 152Tb, 155Tb and 161Tb) which span the entire radiopharmaceutical space (TRNT, PET and SPECT imaging). Since the same element is used, accessing the various diagnostic or therapeutic properties without changing radiochemical procedures and pharmacokinetic properties is advantageous. The use of (heat-sensitive) biomolecules as vector molecule with high affinity and selectivity for a certain molecular target is promising. However, mild radiolabeling conditions are required to prevent thermal degradation of the biomolecule. Herein, we report the evaluation of potential bifunctional chelators for Tb-labeling of heat-sensitive biomolecules using human serum albumin (HSA) to assess the in vivo stability of the constructs. p-SCN-Bn-CHX-A”-DTPA, p-SCN-Bn-DOTA, p-NCS-Bz-DOTA-GA and p-SCN-3p-C-NETA were conjugated to HSA via a lysine coupling method. All HSA-constructs were labeled with [161Tb]TbCl3 at 40°C with radiochemical yields higher than 98%. The radiolabeled constructs were stable in human serum up to 24 h at 37°C. 161Tb-HSA-constructs were injected in mice to evaluate their in vivo stability. Increasing bone accumulation as a function of time was observed for [161Tb]TbCl3 and [161Tb]Tb-DTPA-CHX-A”-Bn-HSA, while negligible bone uptake was observed with the DOTA, DOTA-GA and NETA variants over a 7-day period. The results indicate that the p-SCN-Bn-DOTA, p-NCS-Bz-DOTA-GA and p-SCN-3p-C-NETA are suitable bifunctional ligands for Tb-based radiopharmaceuticals, allowing for high yield radiolabeling in mild conditions.",
keywords = "Terbium-161, Radiopharmaceutical, Radiolabeling, TRNT, Bio-conjugation",
author = "Irwin Cassells and Stephen Ahenkorah and Andrew Burgoyne and {Van de Voorde}, Michiel and Christophe Deroose and Thomas Cardinaels and Guy Bormans and Maarten Ooms and Frederik Cleeren",
note = "Score=10",
year = "2021",
month = aug,
day = "18",
doi = "10.3389/fmed.2021.675122",
language = "English",
volume = "8",
pages = "1--12",
journal = "Frontiers in Medicine",
issn = "2296-858X",
publisher = "Frontiers Media SA",

}

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TY - JOUR

T1 - Radiolabeling of human serum albumin with terbium-161 using mild conditions and evaluation of in vivo Stability

AU - Cassells, Irwin

AU - Ahenkorah, Stephen

AU - Burgoyne, Andrew

AU - Van de Voorde, Michiel

AU - Deroose, Christophe

AU - Cardinaels, Thomas

AU - Bormans, Guy

AU - Ooms, Maarten

AU - Cleeren, Frederik

N1 - Score=10

PY - 2021/8/18

Y1 - 2021/8/18

N2 - Targeted radionuclide therapy (TRNT) is a promising approach for cancer therapy. Terbium has four medically interesting isotopes (149Tb, 152Tb, 155Tb and 161Tb) which span the entire radiopharmaceutical space (TRNT, PET and SPECT imaging). Since the same element is used, accessing the various diagnostic or therapeutic properties without changing radiochemical procedures and pharmacokinetic properties is advantageous. The use of (heat-sensitive) biomolecules as vector molecule with high affinity and selectivity for a certain molecular target is promising. However, mild radiolabeling conditions are required to prevent thermal degradation of the biomolecule. Herein, we report the evaluation of potential bifunctional chelators for Tb-labeling of heat-sensitive biomolecules using human serum albumin (HSA) to assess the in vivo stability of the constructs. p-SCN-Bn-CHX-A”-DTPA, p-SCN-Bn-DOTA, p-NCS-Bz-DOTA-GA and p-SCN-3p-C-NETA were conjugated to HSA via a lysine coupling method. All HSA-constructs were labeled with [161Tb]TbCl3 at 40°C with radiochemical yields higher than 98%. The radiolabeled constructs were stable in human serum up to 24 h at 37°C. 161Tb-HSA-constructs were injected in mice to evaluate their in vivo stability. Increasing bone accumulation as a function of time was observed for [161Tb]TbCl3 and [161Tb]Tb-DTPA-CHX-A”-Bn-HSA, while negligible bone uptake was observed with the DOTA, DOTA-GA and NETA variants over a 7-day period. The results indicate that the p-SCN-Bn-DOTA, p-NCS-Bz-DOTA-GA and p-SCN-3p-C-NETA are suitable bifunctional ligands for Tb-based radiopharmaceuticals, allowing for high yield radiolabeling in mild conditions.

AB - Targeted radionuclide therapy (TRNT) is a promising approach for cancer therapy. Terbium has four medically interesting isotopes (149Tb, 152Tb, 155Tb and 161Tb) which span the entire radiopharmaceutical space (TRNT, PET and SPECT imaging). Since the same element is used, accessing the various diagnostic or therapeutic properties without changing radiochemical procedures and pharmacokinetic properties is advantageous. The use of (heat-sensitive) biomolecules as vector molecule with high affinity and selectivity for a certain molecular target is promising. However, mild radiolabeling conditions are required to prevent thermal degradation of the biomolecule. Herein, we report the evaluation of potential bifunctional chelators for Tb-labeling of heat-sensitive biomolecules using human serum albumin (HSA) to assess the in vivo stability of the constructs. p-SCN-Bn-CHX-A”-DTPA, p-SCN-Bn-DOTA, p-NCS-Bz-DOTA-GA and p-SCN-3p-C-NETA were conjugated to HSA via a lysine coupling method. All HSA-constructs were labeled with [161Tb]TbCl3 at 40°C with radiochemical yields higher than 98%. The radiolabeled constructs were stable in human serum up to 24 h at 37°C. 161Tb-HSA-constructs were injected in mice to evaluate their in vivo stability. Increasing bone accumulation as a function of time was observed for [161Tb]TbCl3 and [161Tb]Tb-DTPA-CHX-A”-Bn-HSA, while negligible bone uptake was observed with the DOTA, DOTA-GA and NETA variants over a 7-day period. The results indicate that the p-SCN-Bn-DOTA, p-NCS-Bz-DOTA-GA and p-SCN-3p-C-NETA are suitable bifunctional ligands for Tb-based radiopharmaceuticals, allowing for high yield radiolabeling in mild conditions.

KW - Terbium-161

KW - Radiopharmaceutical

KW - Radiolabeling

KW - TRNT

KW - Bio-conjugation

UR - https://ecm.sckcen.be/OTCS/llisapi.dll/overview/47457237

U2 - 10.3389/fmed.2021.675122

DO - 10.3389/fmed.2021.675122

M3 - Article

VL - 8

SP - 1

EP - 12

JO - Frontiers in Medicine

JF - Frontiers in Medicine

SN - 2296-858X

M1 - 675122

ER -

ID: 7365060