Ryuichi Nishii1,2, Tatsuya Higashi3,4, Shinya Kagawa1, Chio Okuyama1, Yoshihiko Kishibe1, Masaaki Takahashi1, Tomoko Okina5, Norio Suzuki5, Hiroshi Hasegawa5, Yasuhiro Nagahama6, Koichi Ishizu2,7, Naoya Oishi8, Hiroyuki Kimura9, Hiroyuki Watanabe10, Masahiro Ono10, Hideo Saji10, Hiroshi Yamauchi1. 1. Shiga Medical Center Research Institute, Moriyama, Japan. 2. Dept. of Molecular Imaging and Theranostics, National Institute of Radiological Sciences (NIRS), National Institutes for Quantum and Radiological Science and Technology (QST), Chiba, Japan. 3. Shiga Medical Center Research Institute, Moriyama, Japan. higashi.tatsuya@qst.go.jp. 4. Dept. of Molecular Imaging and Theranostics, National Institute of Radiological Sciences (NIRS), National Institutes for Quantum and Radiological Science and Technology (QST), Chiba, Japan. higashi.tatsuya@qst.go.jp. 5. Dept. of Geriatric Medicine, Shiga General Hospital, Moriyama, Japan. 6. Kawasaki Memorial Hospital, Kawasaki, Japan. 7. Human Health Sciences, Graduate School of Medicine, Kyoto University, Kyoto, Japan. 8. Research and Educational Unit of Leaders for Integrated Medical System, Center for the Promotion of Interdisciplinary Education and Research, Kyoto University, Kyoto, Japan. 9. Dept. of Analytical and Bioinorganic Chemistry, Kyoto Pharmaceutical University, Kyoto, Japan. 10. Dept. of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan.
Abstract
OBJECTIVE: Recently, a benzofuran derivative for the imaging of β-amyloid plaques, 5-(5-(2-(2-(2-18F-fluoroethoxy)ethoxy)ethoxy)benzofuran-2-yl)- N-methylpyridin-2-amine (18F-FPYBF-2) has been validated as a tracer for amyloid imaging and it was found that 18F-FPYBF-2 PET/CT is a useful and reliable diagnostic tool for the evaluation of AD (Higashi et al. Ann Nucl Med, https://doi.org/10.1007/s12149-018-1236-1 , 2018). The aim of this study was to assess the biodistribution and radiation dosimetry of diagnostic dosages of 18F-FPYBF-2 in normal healthy volunteers as a first-in-man study. METHODS: Four normal healthy volunteers (male: 3, female: 1; mean age: 40 ± 17; age range 25-56) were included and underwent 18F-FPYBF-2 PET/CT study for the evaluation of radiation exposure and pharmacokinetics. A 10-min dynamic PET/CT scan of the body (chest and abdomen) was performed at 0-10 min and a 15-min whole-body static scan was performed six times after the injection of 18F-FPYBF-2. After reconstructing PET and CT image data, individual organ time-activity curves were estimated by fitting volume of interest data from the dynamic scan and whole-body scans. The OLINDA/EXM version 2.0 software was used to determine the whole-body effective doses. RESULTS: Dynamic PET imaging demonstrated that the hepatobiliary and renal systems were the principal pathways of clearance of 18F-FPYBF-2. High uptake in the liver and the gall bladder, the stomach, and the kidneys were demonstrated, followed by the intestines and the urinary bladder. The ED for the adult dosimetric model was estimated to be 8.48 ± 1.25 µSv/MBq. The higher absorbed doses were estimated for the liver (28.98 ± 12.49 and 36.21 ± 15.64 µGy/MBq), the brain (20.93 ± 4.56 and 23.05 ± 5.03µ Gy/MBq), the osteogenic cells (9.67 ± 1.67 and 10.29 ± 1.70 µGy/MBq), the small intestines (9.12 ± 2.61 and 11.12 ± 3.15 µGy/MBq), and the kidneys (7.81 ± 2.62 and 8.71 ± 2.90 µGy/MBq) for male and female, respectively. CONCLUSIONS: The ED for the adult dosimetric model was similar to those of other agents used for amyloid PET imaging. The diagnostic dosage of 185-370 MBq of 18F-FPYBF-2 was considered to be acceptable for administration in patients as a diagnostic tool for the evaluation of AD.
OBJECTIVE: Recently, a benzofuran derivative for the imaging of β-amyloid plaques, 5-(5-(2-(2-(2-18F-fluoroethoxy)ethoxy)ethoxy)benzofuran-2-yl)- N-methylpyridin-2-amine (18F-FPYBF-2) has been validated as a tracer for amyloid imaging and it was found that 18F-FPYBF-2 PET/CT is a useful and reliable diagnostic tool for the evaluation of AD (Higashi et al. Ann Nucl Med, https://doi.org/10.1007/s12149-018-1236-1 , 2018). The aim of this study was to assess the biodistribution and radiation dosimetry of diagnostic dosages of 18F-FPYBF-2 in normal healthy volunteers as a first-in-man study. METHODS: Four normal healthy volunteers (male: 3, female: 1; mean age: 40 ± 17; age range 25-56) were included and underwent 18F-FPYBF-2 PET/CT study for the evaluation of radiation exposure and pharmacokinetics. A 10-min dynamic PET/CT scan of the body (chest and abdomen) was performed at 0-10 min and a 15-min whole-body static scan was performed six times after the injection of 18F-FPYBF-2. After reconstructing PET and CT image data, individual organ time-activity curves were estimated by fitting volume of interest data from the dynamic scan and whole-body scans. The OLINDA/EXM version 2.0 software was used to determine the whole-body effective doses. RESULTS: Dynamic PET imaging demonstrated that the hepatobiliary and renal systems were the principal pathways of clearance of 18F-FPYBF-2. High uptake in the liver and the gall bladder, the stomach, and the kidneys were demonstrated, followed by the intestines and the urinary bladder. The ED for the adult dosimetric model was estimated to be 8.48 ± 1.25 µSv/MBq. The higher absorbed doses were estimated for the liver (28.98 ± 12.49 and 36.21 ± 15.64 µGy/MBq), the brain (20.93 ± 4.56 and 23.05 ± 5.03µ Gy/MBq), the osteogenic cells (9.67 ± 1.67 and 10.29 ± 1.70 µGy/MBq), the small intestines (9.12 ± 2.61 and 11.12 ± 3.15 µGy/MBq), and the kidneys (7.81 ± 2.62 and 8.71 ± 2.90 µGy/MBq) for male and female, respectively. CONCLUSIONS: The ED for the adult dosimetric model was similar to those of other agents used for amyloid PET imaging. The diagnostic dosage of 185-370 MBq of 18F-FPYBF-2 was considered to be acceptable for administration in patients as a diagnostic tool for the evaluation of AD.
Authors: Jacoba Alida van de Kreeke; Hoang-Ton Nguyen; Elles Konijnenberg; Jori Tomassen; Anouk den Braber; Mara Ten Kate; Maqsood Yaqub; Bart van Berckel; Adriaan A Lammertsma; Dorret I Boomsma; Stevie H Tan; Frank Verbraak; Pieter Jelle Visser Journal: Br J Ophthalmol Date: 2019-05-22 Impact factor: 4.638
Authors: Jacoba A van de Kreeke; Hoang-Ton Nguyen; Jurre den Haan; Elles Konijnenberg; Jori Tomassen; Anouk den Braber; Mara Ten Kate; Lyduine Collij; Maqsood Yaqub; Bart van Berckel; Adriaan A Lammertsma; Dorret I Boomsma; Hendra Stevie Tan; Frank D Verbraak; Pieter Jelle Visser Journal: Acta Ophthalmol Date: 2019-05-06 Impact factor: 3.761
Authors: Jacoba A van de Kreeke; Hoang Ton Nguyen; Elles Konijnenberg; Jori Tomassen; Anouk den Braber; Mara Ten Kate; Maqsood Yaqub; Bart van Berckel; Adriaan A Lammertsma; Dorret I Boomsma; H Stevie Tan; Pieter Jelle Visser; Frank D Verbraak Journal: Acta Ophthalmol Date: 2020-10-18 Impact factor: 3.761