In-vitro interaction studies between the amyloid PET tracer florbetaben and the amyloid-beta targeting antibodies lecanemab and donanemab on AD brain samples reveal no interferences.

BACKGROUND

Amyloid PET imaging enables the in vivo visualization and quantification of amyloid-beta deposits in the brain. In research and clinical settings, it is further used to monitor amyloid-beta burden as well as the biological response to disease-modifying therapies. Amyloid-beta targeting monoclonal antibodies (mAbs) such as lecanemab and donanemab were designed to reduce brain amyloid-beta burden. If the PET tracer and the mAbs would bind to the same site, the PET signal may be impacted in patients undergoing therapy. Binding interaction studies were conducted to verify the reliability of PET readouts in this setting. The aim of this study was to investigate whether lecanemab or donanemab interfere with the binding of the amyloid PET tracer florbetaben to aggregated amyloid-beta deposits in vitro.

METHODS

Human Alzheimer’s disease (AD) brain tissue from various sources was used to assess potential interactions between florbetaben and lecanemab or donanemab. Three complementary approaches were used to confirm target binding and to study potential interactions: (1) competitive immunohistochemistry (IHC), (2) competitive autoradiography (ARG), and (3) ligand binding assays (LBA).

RESULTS

Across all three sets of experiments, no evidence of competition or inhibition of florbetaben binding to amyloid-beta deposits by lecanemab or donanemab was observed. Autoradiography demonstrated robust tracer binding to amyloid-beta plaques that was unaffected by incubation with excess antibody. Similarly, IHC and LBA experiments confirmed that florbetaben and the tested mAbs target distinct binding sites on amyloid-beta aggregates.

CONCLUSIONS

These results demonstrate that neither lecanemab nor donanemab interfere with florbetaben binding to amyloid-beta plaques in vitro, further validating its use in this setting. While the current data are limited to in-vitro experiments, they further support the use of florbetaben PET for monitoring amyloid-beta changes during treatment with amyloid-beta targeting therapies.