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

Autor: Senda M; Division of Molecular Imaging, Institute of Biomedical Research and Innovation, Kobe, Japan., Brooks DJ, Farrar G, Somer EJ, Paterson CL, Sasaki M, McParland BJ
Jazyk: angličtina
Zdroj: Annals of nuclear medicine [Ann Nucl Med] 2015 Aug; Vol. 29 (7), pp. 627-35. Date of Electronic Publication: 2015 Jun 05.
DOI: 10.1007/s12149-015-0986-2
Abstrakt: Objectives: The Phase I safety, biodistribution and internal radiation dosimetry study in adult healthy Japanese males of flutemetamol ((18)F) 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 (18)F activity concentrations in whole blood and plasma and high-performance liquid chromatography (HPLC) established the percentages of parent [(18)F]flutemetamol and its metabolites. Voided urine activity was recorded. The decay-corrected and normalised (18)F 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 [(18)F]flutemetamol.
Results: Flutemetamol ((18)F) 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 (18)F radioactivity was in the form of parent [(18)F]flutemetamol, reducing to 8 and 2% at 25 and 90 min, respectively, giving rise to less lipophilic (18)F-labelled metabolites. Comparisons with the Caucasian cohort showed no differences that could be regarded as clinically significant.
Conclusion: The clinical safety of [(18)F]flutemetamol demonstrated no differences of clinical significance in the pharmacokinetics, biodistribution and internal radiation dosimetry profiles between Caucasian and Japanese adults.
Databáze: MEDLINE
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