Preparation and Preliminary Evaluation of 18F-BHPI as a Novel PET Probe Targeting Estrogen Receptor Alpha (ERα)
- 1Department of Nuclear Medicine, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361003, China
- 2School of Public Health, Xiamen University, Xiamen 361102, China
Abstract
Estrogen receptor alpha (ERα) is an important molecular target for the diagnosis and endocrine therapy of breast cancer. BHPI is a recently identified class of novel non-steroidal ERα-targeting small molecules; however，no studies on its radiolabeling or molecular imaging applications have been reported to date. In this study，a boronic ester precursor of BHPI (B-BHPI) was designed and synthesized，and the PET molecular probe 18F-BHPI was successfully prepared via a copper-mediated nucleophilic radiofluorination strategy. The radiochemical properties, in vitro stability，cellular uptake characteristics，and in vivo biodistribution of the probe were systematically evaluated. The results showed that 18F-BHPI was obtained with a radiochemical conversion (RCC) of (37.75±7.39)%，a radiochemical yield (RCY) of (6.28±0.15)%，a radiochemical purity (RCP) of (96.38±1.62)%，and a molar activity of (0.29±0.11) GBq/μmol. The LogP value was 1.10±0.27. The probe exhibited excellent stability in both saline and mouse serum，remaining predominantly intact after 240 min of incubation. Cellular uptake studies demonstrated significantly higher accumulation of 18F-BHPI in ERα-positive MCF-7 cells than in ERα-negative MDA-MB-231 cells. Competitive inhibition experiments further revealed that tamoxifen，17β-estradiol，and BHPI markedly reduced probe uptake in MCF-7 cells，with BHPI showing the strongest blocking effect. Biodistribution studies in normal female SD rats indicated that 18F-BHPI was mainly metabolized through the hepatobiliary and intestinal pathways and displayed a well-defined in vivo distribution and clearance profile. To the best of our knowledge，this study represents the first successful radiolabeling of BHPI and the first construction of a BHPI-based molecular imaging probe. The resulting 18F-BHPI exhibited favorable physicochemical properties and ERα-related uptake characteristics，providing a useful tool for in vivo tracing of BHPI and a promising foundation for the development of novel ERα-related PET molecular probes.
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BibTeX
@article{yesen2026preparation,
title = {{Preparation and Preliminary Evaluation of 18F-BHPI as a Novel PET Probe Targeting Estrogen Receptor Alpha (ERα)}},
author = {Yesen LI and Xueqi WANG and Yike WANG and Yuejing DENG and Xinying ZENG and Zhide GUO},
journal = {Journal of Isotopes},
year = {2026},
month = oct,
doi = {10.7538/tws.2026.youxian.057},
url = {https://doi.org/10.7538/tws.2026.youxian.057},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Preparation and Preliminary Evaluation of 18F-BHPI as a Novel PET Probe Targeting Estrogen Receptor Alpha (ERα)
AU - Yesen LI
AU - Xueqi WANG
AU - Yike WANG
AU - Yuejing DENG
AU - Xinying ZENG
AU - Zhide GUO
PY - 2026
DA - 2026/10/26
JO - Journal of Isotopes
DO - 10.7538/tws.2026.youxian.057
UR - https://doi.org/10.7538/tws.2026.youxian.057
AB - Estrogen receptor alpha (ERα) is an important molecular target for the diagnosis and endocrine therapy of breast cancer. BHPI is a recently identified class of novel non-steroidal ERα-targeting small molecules; however，no studies on its radiolabeling or molecular imaging applications have been reported to date. In this study，a boronic ester precursor of BHPI (B-BHPI) was designed and synthesized，and the PET molecular probe 18F-BHPI was successfully prepared via a copper-mediated nucleophilic radiofluorination strategy. The radiochemical properties, in vitro stability，cellular uptake characteristics，and in vivo biodistribution of the probe were systematically evaluated. The results showed that 18F-BHPI was obtained with a radiochemical conversion (RCC) of (37.75±7.39)%，a radiochemical yield (RCY) of (6.28±0.15)%，a radiochemical purity (RCP) of (96.38±1.62)%，and a molar activity of (0.29±0.11) GBq/μmol. The LogP value was 1.10±0.27. The probe exhibited excellent stability in both saline and mouse serum，remaining predominantly intact after 240 min of incubation. Cellular uptake studies demonstrated significantly higher accumulation of 18F-BHPI in ERα-positive MCF-7 cells than in ERα-negative MDA-MB-231 cells. Competitive inhibition experiments further revealed that tamoxifen，17β-estradiol，and BHPI markedly reduced probe uptake in MCF-7 cells，with BHPI showing the strongest blocking effect. Biodistribution studies in normal female SD rats indicated that 18F-BHPI was mainly metabolized through the hepatobiliary and intestinal pathways and displayed a well-defined in vivo distribution and clearance profile. To the best of our knowledge，this study represents the first successful radiolabeling of BHPI and the first construction of a BHPI-based molecular imaging probe. The resulting 18F-BHPI exhibited favorable physicochemical properties and ERα-related uptake characteristics，providing a useful tool for in vivo tracing of BHPI and a promising foundation for the development of novel ERα-related PET molecular probes.
SN - 1000-7512
ER -