Automated radiosynthesis and biodistribution of [¹⁸F]fluoroflutamide.
4 affiliations
- 1Division of Nuclear Medicine, Department of Radiology, University of Michigan Medical School, Ann Arbor, MI, 48109, USA.
- 2Division of Nuclear Medicine, Department of Radiology, University of Michigan Medical School, Ann Arbor, MI, 48109, USA. [email protected].
- 3The Interdepartmental Program in Medicinal Chemistry, University of Michigan, Ann Arbor, MI, 48109, USA. [email protected].
- 4Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA. [email protected].
Abstract
Background
The androgen receptor (AR) is upregulated in multiple cancers, such as salivary gland cancer, glioblastoma, triple-negative breast cancer, and, most commonly, prostate cancer. Imaging expression of the AR using a radiolabeled AR antagonist would enable non-invasive clinical staging and assessment of tumor heterogeneity via positron emission tomography (PET), complementing the findings of a [⁶⁸Ga]PSMA-11 scan. Previous efforts described the radiolabeling of enzalutamide with fluorine-18 but were limited by low molar activity. In this study, we showcase an efficient, reproducible automated synthesis of [¹⁸F]fluoroflutamide via zinc-mediated radiofluorination and assess its biodistribution in preclinical models of prostate cancer.Results
From 1.87 Ci (69.19 GBq) of [¹⁸F]fluoride, [¹⁸F]fluoroflutamide was isolated with a non-decay-corrected radiochemical yield of 3.46 ± 1.30% (n = 4) and a radiochemical purity of > 99% in an average 79 min from end-of-beam using a bromoamide precursor. The average Am was 1.57 Ci/µmol (or 58.23 GBq/µmol) at the end of synthesis, and the radiochemical purity after 4 h was > 97%, indicating negligible radiolysis. A biodistribution and imaging study was performed using nude athymic mice with 22Rv1 human prostate cancer xenografts. From the results of this study, we observed a 'mass effect' in which carrier-added mice displayed an increased uptake of the tracer across most organs.Conclusions
Herein, we report the optimized automated radiosynthesis of [¹⁸F]fluoroflutamide with high purity and sufficient yield for preclinical evaluation of AR-targeted imaging in mouse models of prostate cancer. The lack of uptake in androgen receptor-rich tissues and xenografts suggests impaired in vivo target engagement. While α-tertiary fluorination may attenuate CYP1A2-mediated oxidation to the higher-affinity 2-hydroxyflutamide metabolite, the observed signal is also consistent with reduced intrinsic AR affinity and/or altered pharmacokinetics of the fluorinated analog.
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BibTeX
@article{kaup2026automated,
title = {{Automated radiosynthesis and biodistribution of [¹⁸F]fluoroflutamide.}},
author = {Gina Kaup and Jason Anthony Witek and Shelbie Jaylene Cingoranelli and Jenelle Stauff and David Raffel and Allen Frederick Brooks and Peter James Henry Scott and Jay Samuel Wright},
journal = {EJNMMI radiopharmacy and chemistry},
year = {2026},
month = jul,
doi = {10.1186/s41181-026-00453-z},
url = {https://europepmc.org/article/MED/42894110},
note = {CC BY},
}
RIS
TY - JOUR
TI - Automated radiosynthesis and biodistribution of [¹⁸F]fluoroflutamide.
AU - Gina Kaup
AU - Jason Anthony Witek
AU - Shelbie Jaylene Cingoranelli
AU - Jenelle Stauff
AU - David Raffel
AU - Allen Frederick Brooks
AU - Peter James Henry Scott
AU - Jay Samuel Wright
PY - 2026
DA - 2026/07/01
JO - EJNMMI radiopharmacy and chemistry
DO - 10.1186/s41181-026-00453-z
UR - https://europepmc.org/article/MED/42894110
AB - Background The androgen receptor (AR) is upregulated in multiple cancers, such as salivary gland cancer, glioblastoma, triple-negative breast cancer, and, most commonly, prostate cancer. Imaging expression of the AR using a radiolabeled AR antagonist would enable non-invasive clinical staging and assessment of tumor heterogeneity via positron emission tomography (PET), complementing the findings of a [⁶⁸Ga]PSMA-11 scan. Previous efforts described the radiolabeling of enzalutamide with fluorine-18 but were limited by low molar activity. In this study, we showcase an efficient, reproducible automated synthesis of [¹⁸F]fluoroflutamide via zinc-mediated radiofluorination and assess its biodistribution in preclinical models of prostate cancer.Results From 1.87 Ci (69.19 GBq) of [¹⁸F]fluoride, [¹⁸F]fluoroflutamide was isolated with a non-decay-corrected radiochemical yield of 3.46 ± 1.30% (n = 4) and a radiochemical purity of > 99% in an average 79 min from end-of-beam using a bromoamide precursor. The average Am was 1.57 Ci/µmol (or 58.23 GBq/µmol) at the end of synthesis, and the radiochemical purity after 4 h was > 97%, indicating negligible radiolysis. A biodistribution and imaging study was performed using nude athymic mice with 22Rv1 human prostate cancer xenografts. From the results of this study, we observed a 'mass effect' in which carrier-added mice displayed an increased uptake of the tracer across most organs.Conclusions Herein, we report the optimized automated radiosynthesis of [¹⁸F]fluoroflutamide with high purity and sufficient yield for preclinical evaluation of AR-targeted imaging in mouse models of prostate cancer. The lack of uptake in androgen receptor-rich tissues and xenografts suggests impaired in vivo target engagement. While α-tertiary fluorination may attenuate CYP1A2-mediated oxidation to the higher-affinity 2-hydroxyflutamide metabolite, the observed signal is also consistent with reduced intrinsic AR affinity and/or altered pharmacokinetics of the fluorinated analog.
SN - 2365-421X
ER -