Despite the application of amyloid imaging agents such as PIB, SB13, and FDDNP in Alzheimer's disease (AD) patients, the successful use of these agents in transgenic mice models of AD has not been reported to date. As a first step in understanding the behaviour of these ligands in transgenic models of AD, we have investigated in a series of in vitro ligand binding assays the interaction of selected agents, including PIB, FDDNP, SB13, and BSB, with amyloid fibrils produced from rodent A beta(1-40) (roA beta) peptide. The data indicate that the ligand binding affinities together with the pattern and number of binding sites on the roA beta fibrils are broadly conserved with that reported previously for human A beta(1-40) (huA beta) fibrils. However, characterisation of huA beta fibrils formed in the presence of increasing amounts of roA beta (1, 5, 10% w/w) demonstrated a dose-dependent reduction in the number of high affinity [H-3]Me-BTA-1 binding sites such that at the highest amount of roA beta the specific signal was reduced by similar to 95%. These studies suggest that (i) the presence of small amounts of roA beta in huA beta fibrils has the potential to cause subtle ultrastructural alterations in the polymers and (ii) the weak binding signal observed in vivo in the transgenic mouse models of AD may in part be due to the decreased number of high affinity binding sites on the A beta fibrils. beta 2006 Elsevier Inc. All rights reserved.