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Annals of Nuclear Medicine
Published in: Annals of Nuclear Medicine 7/2015

Open Access 01-08-2015 | Original Article

The clinical safety, biodistribution and internal radiation dosimetry of flutemetamol (18F) injection in healthy Japanese adult volunteers

Authors: Michio Senda, David J. Brooks, Gill Farrar, Edward J. Somer, Carolyn L. Paterson, Masahiro Sasaki, Brian J. McParland

Published in: Annals of Nuclear Medicine | Issue 7/2015

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Abstract

Objectives

The Phase I safety, biodistribution and internal radiation dosimetry study in adult healthy Japanese males of flutemetamol (18F) injection, an in vivo β-amyloid imaging agent, is reported and compared with previously obtained Caucasian data.

Methods

Whole-body PET scans of 6 healthy volunteers (age 51.8–61.7 years) were acquired approximately 4 h post-injection (administered activity 102–160 MBq). Venous blood sampling determined 18F activity concentrations in whole blood and plasma and high-performance liquid chromatography (HPLC) established the percentages of parent [18F]flutemetamol and its metabolites. Voided urine activity was recorded. The decay-corrected and normalised 18F activity of 14 source organ regions as a function of time was entered into the OLINDA/EXM software to calculate the internal radiation dosimetry and effective dose of each subject following the MIRD schema. The pharmacokinetics, biodistribution and dosimetry profiles were compared to data obtained from a cohort of healthy Caucasian adult volunteers from a previous Phase I study of [18F]flutemetamol.

Results

Flutemetamol (18F) injection was well tolerated. The highest mean initial uptakes were measured in the liver (15.2 %), lungs (10.2 %) and brain (6.6 %). The highest mean radiation absorbed doses were received by the gallbladder wall (366 μGy/MBq), upper large intestine (138 μGy/MBq) and small intestine (121 μGy/MBq). The mean effective dose was 34.9 μSv/MBq. HPLC analysis demonstrated that at 5-min post-injection about 75 % of plasma 18F radioactivity was in the form of parent [18F]flutemetamol, reducing to 8 and 2 % at 25 and 90 min, respectively, giving rise to less lipophilic 18F-labelled metabolites. Comparisons with the Caucasian cohort showed no differences that could be regarded as clinically significant.

Conclusion

The clinical safety of [18F]flutemetamol demonstrated no differences of clinical significance in the pharmacokinetics, biodistribution and internal radiation dosimetry profiles between Caucasian and Japanese adults.
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Metadata
Title
The clinical safety, biodistribution and internal radiation dosimetry of flutemetamol (18F) injection in healthy Japanese adult volunteers
Authors
Michio Senda
David J. Brooks
Gill Farrar
Edward J. Somer
Carolyn L. Paterson
Masahiro Sasaki
Brian J. McParland
Publication date
01-08-2015
Publisher
Springer Japan
Published in
Annals of Nuclear Medicine / Issue 7/2015
Print ISSN: 0914-7187
Electronic ISSN: 1864-6433
DOI
https://doi.org/10.1007/s12149-015-0986-2

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