Development and comparative pharmacokinetic evaluation of iodine-125- and fluorine-18-labelled analogues of 4-(benzo[d]thiazol-2-yl)phenylboronic acid for boron neutron capture therapy
- 1Division of Applied RI, Korea Institute of Radiological & Medical Sciences (KIRAMS) 75 Nowon-ro, Nowon-gu Seoul 01812 Republic of Korea [email protected] [email protected].
- 2Radiological and Medico-Oncological Sciences, University of Science and Technology (UST) 217, Gajeong-ro, Yuseong-gu Daejeon 34113 Republic of Korea.
Abstract
Boron neutron capture therapy (BNCT) requires accurate assessment of boron biodistribution to support treatment planning. Radiolabelled analogues of 4-(benzo[d]thiazol-2-yl)phenylboronic acid (BTPB) were developed to investigate how radiohalogen substitution influences in vivo distribution and to explore their potential for imaging BTPB-related distribution characteristics. The aryl boronic acid moiety of BTPB was replaced with iodine-125 through copper-mediated iododeboronation to generate [¹²⁵I]IPBT, or with fluorine-18 through copper-mediated nucleophilic radiofluorination to produce [¹⁸F]FPBT. Iododeboronation afforded [¹²⁵I]IPBT with an isolated radiochemical yield of 28.39 ± 5.12%, whereas radiofluorination afforded [¹⁸F]FPBT with a lower decay-corrected isolated yield of 3.10 ± 1.35%. Despite comparable radiochemical purity, lipophilicity, and in vitro radiolabel stability, the two analogues showed distinct in vivo distribution profiles. Biodistribution analysis showed that [¹⁸F]FPBT exhibited selected temporal distribution characteristics relevant to BTPB imaging, including early brain uptake and a time-dependent increase in tumour-to-brain contrast, whereas [¹²⁵I]IPBT showed a distinct organ distribution pattern consistent with possible in vivo deiodination. In an orthotopic glioblastoma model, [¹⁸F]FPBT and BTPB exhibited a qualitatively similar directional change toward increased tumour-to-brain contrast within their respective observation periods. However, because the two compounds were evaluated using different administered masses, analytical methods, and sampling intervals, these findings do not establish pharmacokinetic equivalence. These results demonstrate that radiohalogen substitution substantially influences the in vivo behaviour of BTPB-derived analogues and support further investigation of [¹⁸F]FPBT as a candidate positron emission tomography imaging analogue for assessing intracranial distribution characteristics relevant to BTPB. Validation under matched experimental conditions is required to determine whether [¹⁸F]FPBT can quantitatively reflect BTPB-derived boron distribution.
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BibTeX
@article{im2026development,
title = {{Development and comparative pharmacokinetic evaluation of iodine-125- and fluorine-18-labelled analogues of 4-(benzo[d]thiazol-2-yl)phenylboronic acid for boron neutron capture therapy}},
author = {Changkeun Im and Mah Rukh Zia and Iqra Bibi and Kyung Jun Kang and Jung Young Kim and Ho Young Kim and Ji-Ae Park},
journal = {RSC advances},
year = {2026},
month = nov,
doi = {10.1039/d6ra07719f},
url = {https://europepmc.org/article/PMC/PMC13725790},
note = {CC BY},
}
RIS
TY - JOUR
TI - Development and comparative pharmacokinetic evaluation of iodine-125- and fluorine-18-labelled analogues of 4-(benzo[d]thiazol-2-yl)phenylboronic acid for boron neutron capture therapy
AU - Changkeun Im
AU - Mah Rukh Zia
AU - Iqra Bibi
AU - Kyung Jun Kang
AU - Jung Young Kim
AU - Ho Young Kim
AU - Ji-Ae Park
PY - 2026
DA - 2026/11/02
JO - RSC advances
DO - 10.1039/d6ra07719f
UR - https://europepmc.org/article/PMC/PMC13725790
AB - Boron neutron capture therapy (BNCT) requires accurate assessment of boron biodistribution to support treatment planning. Radiolabelled analogues of 4-(benzo[d]thiazol-2-yl)phenylboronic acid (BTPB) were developed to investigate how radiohalogen substitution influences in vivo distribution and to explore their potential for imaging BTPB-related distribution characteristics. The aryl boronic acid moiety of BTPB was replaced with iodine-125 through copper-mediated iododeboronation to generate [¹²⁵I]IPBT, or with fluorine-18 through copper-mediated nucleophilic radiofluorination to produce [¹⁸F]FPBT. Iododeboronation afforded [¹²⁵I]IPBT with an isolated radiochemical yield of 28.39 ± 5.12%, whereas radiofluorination afforded [¹⁸F]FPBT with a lower decay-corrected isolated yield of 3.10 ± 1.35%. Despite comparable radiochemical purity, lipophilicity, and in vitro radiolabel stability, the two analogues showed distinct in vivo distribution profiles. Biodistribution analysis showed that [¹⁸F]FPBT exhibited selected temporal distribution characteristics relevant to BTPB imaging, including early brain uptake and a time-dependent increase in tumour-to-brain contrast, whereas [¹²⁵I]IPBT showed a distinct organ distribution pattern consistent with possible in vivo deiodination. In an orthotopic glioblastoma model, [¹⁸F]FPBT and BTPB exhibited a qualitatively similar directional change toward increased tumour-to-brain contrast within their respective observation periods. However, because the two compounds were evaluated using different administered masses, analytical methods, and sampling intervals, these findings do not establish pharmacokinetic equivalence. These results demonstrate that radiohalogen substitution substantially influences the in vivo behaviour of BTPB-derived analogues and support further investigation of [¹⁸F]FPBT as a candidate positron emission tomography imaging analogue for assessing intracranial distribution characteristics relevant to BTPB. Validation under matched experimental conditions is required to determine whether [¹⁸F]FPBT can quantitatively reflect BTPB-derived boron distribution.
SN - 2046-2069
ER -