Chau WF, Peterson S, Farrar G, Eko-Ebongue S, Barnes C.
Evaluation of metabolites of [18F]flutemetamol, an amyloid imaging agent in human and rat in vitro and rat in vivo models.
Human Amyloid Imaging 2010 Meeting Abstracts. 2010 April 9;
[18F]flutemetamol is an 18F-labeled derivative of PIB that shows affinity for beta-amyloid, a characteristic of the
pathology in Alzheimer’s disease (AD) that develops before clinical manifestation of AD. [18F]flutemetamol in AD
patients shows significantly greater uptake in neocortical and striatum regions compared with healthy volunteers
(HV) and distributes in a comparable manner to the [11C]PIB tracer, but has the advantage of a longer half-life.
[18F]flutemetamol is a small lipophillic tracer with good brain uptake of 4% injected dose (id) at 2 minutes postinjection
Metabolites identified in pre-clinical work are primarily more hydrophilic than flutemetamol itself. Human,
dog, mouse and rat hepatic S9 incubations have been carried out on 18F and 14C-radiolabelled flutemetamol
compounds for up to 180 minutes. Small quantities of two to four metabolites were observed in these in vitro
assays. N-demethylation was considered the main metabolic pathway and the resulting metabolite was present in
both the rat and human systems.
In vivo evaluation of [11C]flutemetamol in baboons and rats resulted in two hydrophilic metabolites in both species.
[3H]flutemetamol was also tested in human and rat plasma in vitro studies, generating small quantities of two
Analysis of arterial blood samples from subjects in the ALZ103 clinical trials, showed rapid metabolism of [18F]
flutemetamol at 20 minutes pi. These data are compared with in vivo rat studies to establish if any metabolites
formed cross the blood-brain barrier (BBB).
An understanding of metabolism in preclinical and human subjects is important so that any transfer of metabolites
across the BBB can be assessed with regards to appropriate kinetic modelling. In the case of imaging amyloid,
this could be valuable in potentially improving the accuracy of image interpretation, especially in subjects close to the threshold of normality and abnormality.