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

OBJECTIVES: The Phase I safety, biodistribution and internal radiation dosimetry study in adult healthy Japanese males of flutemetamol ((18)F) injection, an in vivo ß-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.