Biodistribution and radiation dosimetry of D-isomer of 4-borono-2-[18F]fluoro-phenylalanine: A comparative PET/CT study with L-isomer in healthy human volunteers

Qiao Yang; Wenjia Zhu; Chao Ren; Hongfeng Ji; Dongchun Wang; Yu Liu; Fang Li; Yanrong Du; Yuanhao Liu; Li Huo

doi:10.1016/j.nucmedbio.2020.12.006

Biodistribution and radiation dosimetry of D-isomer of 4-borono-2-[¹⁸F]fluoro-phenylalanine: A comparative PET/CT study with L-isomer in healthy human volunteers

Nucl Med Biol. 2021 Mar-Apr:94-95:32-37. doi: 10.1016/j.nucmedbio.2020.12.006. Epub 2021 Jan 8.

Authors

Qiao Yang¹, Wenjia Zhu¹, Chao Ren¹, Hongfeng Ji², Dongchun Wang², Yu Liu¹, Fang Li¹, Yanrong Du³, Yuanhao Liu⁴, Li Huo⁵

Affiliations

¹ Department of Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine, Beijing, China.
² Neuboron Medtech Ltd., Nanjing, China.
³ Department of Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine, Beijing, China. Electronic address: 13651331609@139.com.
⁴ Neuboron Medtech Ltd., Nanjing, China. Electronic address: yhl.taiwan@gmail.com.
⁵ Department of Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine, Beijing, China. Electronic address: huoli@pumch.cn.

PMID: 33486437
DOI: 10.1016/j.nucmedbio.2020.12.006

Abstract

Introduction: L-isomer of 4-borono-2-¹⁸F-fluoro-phenylalanine (L-[¹⁸F]FBPA) was generally applied in clinic for boron neutron capture therapy (BNCT). With radiotracer validation, D-isomer of [¹⁸F]FBPA (D-[¹⁸F]FBPA) was found a higher tumor to normal brain tissue ratio (TBR) than its L-isomer on positron emission tomography (PET) in rat brain glioma. The present study was conducted as a first-in-human study to explore the biodistribution and radiation dosimetry of D-[¹⁸F]FBPA in healthy human volunteers, compared with L-[¹⁸F]FBPA.

Methods: D-[¹⁸F]FBPA or L-[¹⁸F]FBPA was injected intravenously. Five whole-body PET scans were performed for each subject in the next 2 h. Organ time-activity curves were drawn by measuring SUV_mean in volumes of interest. Absorbed dose coefficient of target organs and effective dose (ED) were estimated on OLINDA/EXM.

Results: Two healthy volunteers (both males) and three healthy volunteers (2 males, 1 female) were intravenously injected with D-[¹⁸F]FBPA (5.5-7.2 MBq/kg) and L-[¹⁸F]FBPA (3.9-6.8 MBq/kg) respectively. Only limited accumulation of D-[¹⁸F]FBPA was observed in healthy human brain, pancreas, liver, spleen and skeleton. The ED was calculated to be 0.026 mSv/MBq. Urinary bladder wall received the highest dose of 0.28 mGy/MBq, followed by kidneys (0.06 mGy/MBq), and all the other organs received less than 0.03 mGy/MBq. For L-[¹⁸F]FBPA, higher uptake in brain, pancreas, liver, spleen and skeleton could be visualized, compared with D-[¹⁸F]FBPA. The ED of L-[¹⁸F]FBPA was 0.020 ± 0.001 mSv/MBq. Urinary bladder wall and kidneys still received the highest dose among organs but with lower values than those of D-[¹⁸F]FBPA.

Conclusions: D-[¹⁸F]FBPA had lower activity in normal brain, liver, spleen, pancreas and skeleton, compared with its L-isomer. D-[¹⁸F]FBPA is safe from a radiological standpoint.

Advances in knowledge and implications for patient care: D-[¹⁸F]FBPA was safe from a radiological standpoint, and had lower activity in normal brain, liver, spleen, pancreas and skeleton than its L-isomer. This study ensures the safety and validity of D-[¹⁸F]FBPA for further clinical trials in patients with cancer.

Keywords: BNCT; Biodistribution; D-[(18)F]FBPA; PET; Radiation dosimetry.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Female
Fluorine Radioisotopes*
Healthy Volunteers*
Humans
Male
Phenylalanine / chemistry*
Phenylalanine / pharmacokinetics*
Positron Emission Tomography Computed Tomography*
Radiometry
Stereoisomerism
Tissue Distribution

Substances

Fluorine Radioisotopes
Phenylalanine
Fluorine-18