An exploratory efficacy study of the amyloid imaging agent [(18)F]flutemetamol in Japanese Subjects.

Abstract

The aim of the study presented was to investigate the brain uptake properties of the amyloid PET agent [(18)F]flutemetamol in Japanese healthy controls and clinically probable Alzheimer's disease (AD) patients, and to make a comparison with the results of a previously performed study on Caucasian subjects. [(18)F]flutemetamol was recently approved by the American Food and Drug Administration and the European Medicines Agency for visualization of amyloid in vivo. Since the first clinical study of [(18)F]flutemetamol-an (18)F derivative of the PET tracer 11C-Pittsburgh Compound B targeting β-amyloid--took place, several clinical studies have been performed, but few focusing on a Japanese population. In the Step A, three elderly healthy volunteers and three AD subjects underwent dynamic PET scanning 0-30 and 60-150min after injection of 185MBq [(18)F]flutemetamol. The brain volume of distribution (VT) was quantified using Logan's linear graphical analysis and as standardized uptake value ratios (SUVR) with a cerebellar reference. The optimal acquisition window was determined from brain time activity curves for Step B. In the Step B, 5 AD and 5 elderly healthy volunteers were scanned from 80 to 140min after intravenous injection of [(18)F]flutemetamol. The data from the two parts were pooled for estimation of overall efficacy. [(18)F]Flutemetamol injection was shown to be safe-no serious adverse events were reported during this study. A simplified SUVR estimate of the uptake of [(18)F]flutemetamol using a time window of 85-115min post injection successfully discriminated AD cases from healthy volunteers. AD subjects showed an elevated tracer uptake in prefrontal cortex, the lateral temporal cortex and precuneus amongst other regions. No significant [(18)F]flutemetamol PET differences could be seen between the Japanese AD cases in this study and those from an earlier Caucasian study, or between control subjects in Japanese and Caucasian studies. This study supports the use of [(18)F]flutemetamol PET in Japanese population as a marker of the presence of fibrillar β-amyloid. The lack of differences between the Japanese cohort and those from a previous Caucasian cohort supports the extrapolation of results from other Caucasian [(18)F]flutemetamol PET studies to the Japanese population.