18F-FPYBF-2, a new F-18 labelled amyloid imaging PET tracer: biodistribution and radiation dosimetry assessment of first-in-man 18F-FPYBF-2 PET imaging
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.
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.
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.
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.
KeywordsAlzheimer disease Amyloid imaging Normal healthy volunteers Positron emission tomography Biodistributtion Radiation dosimetry OLINDA/EXM
This work was supported by the Japan Society for the Promotion of Science (JSPS) through the “Funding Program for Next Generation World-Leading Researchers (NEXT Program, LS060),” initiated by the Council for Science and Technology Policy (CSTP).
Compliance with ethical standards
Conflict of interest
No potential conflicts of interest were disclosed with regard to this study.
- 1.Alzheimer Disease International. World Alzheimer Report 2016. 2016. https://www.alz.co.uk/research/WorldAlzheimerReport2016.pdf. Accessed 9 July 2017.
- 3.Kudo Y, Okamura N, Furumoto S, Tashiro M, Furukawa K, Maruyama M, et al. 2-(2-[2-Dimethylaminothiazol-5-yl]Ethenyl)-6-(2-[Fluoro]Ethoxy) Benzoxazole: a novel PET agent for in vivo detection of dense amyloid plaques in Alzheimer’s disease patients. J Nucl Med. 2007;48:553 – 61.CrossRefPubMedGoogle Scholar
- 12.Higashi T, Nishii R, Kagawa S, Kishibe Y, Takahashi M, Okina T, et al. 18F-FPYBF-2, a new F-18 labelled amyloid imaging PET tracer - First-in-man volunteer study and clinical evaluation of patients with dementia. Ann Nucl Med. 2018. https://doi.org/10.1007/s12149-018-1236-1.PubMedCentralGoogle Scholar
- 17.ICRP, 2007. The 2007 Recommendations of the International Commission on Radiological Protection. ICRP Publication 103. Ann ICRP 37 (2–4).Google Scholar
- 22.ICRP Radiation dose to patients from radiopharmaceuticals: a compendium of current information related to frequently used substances. 2015. ICRP Publication 128. Ann. ICRP 44(2S).Google Scholar
- 24.Macey D, Williams L, Breitz H, Liu A, Johnson T, Zanzonico P. A primer for radioimmunotherapy and radionuclide therapy. AAPM Rep. 2001;71. https://www.aapm.org/pubs/reports/rpt_71.pdf.