in vivo evaluation of the stabilities of 52Mn-DOTA and 64Cu-DOTA using radiolabelled liposomes and PET imaging]]>

摘要

AbstractLiposomes are nanoparticles used in drug delivery that distribute over several days in humans and larger animals. Radiolabeling with long-lived positron emission tomography (PET) radionuclides, such as manganese-52 (52Mn, T?=5.6days), allow the imaging of this biodistribution. We report optimized protocols for radiolabeling liposomes with52Mn, through both remote-loading and surface labeling. For comparison, liposomes were also remote-loaded and surface labeled with copper-64 (64Cu, T?=12.7h) through conventional means. The chelator DOTA was used in all cases. Thein vivostability of radiometal chelates is widely debated but studies that mimic a realisticin vivosetting are lacking. Therefore, we employed these four radiolabeled liposome types as platforms to demonstrate a new concept for suchin vivoevaluation, here of the chelates52Mn-DOTA and64Cu-DOTA. This was done by comparing “shielded” remote-loaded with “exposed” surface labeled variants in a CT26 tumor-bearing mouse model. Remote loading (90min at 55°C) and surface labeling (55°C for 2h) of52Mn gave excellent radiolabeling efficiencies of 97–100% and 98–100% respectively, and the liposome biodistribution was imaged by PET for up to 8days. Liposomes with surface-conjugated52Mn-DOTA exhibited a significantly shorter plasma half-life (T?=14.4h) when compared to the remote-loaded counterpart (T?=21.3h