AG73-modified Bubble liposomes for targeted ultrasound imaging of tumor neovasculature

Ultrasound imaging is a widely used imaging technique. The use of contrast agents has become an indispensible part of clinical ultrasound imaging, and molecular imaging via ultrasound has recently attracted significant attention. We recently reported that Bubble liposomes (BLs) encapsulating US imaging gas liposomes were suitable for ultrasound imaging and gene delivery. The 12 amino acid AG73 peptide derived from the laminin alpha 1 chain is a ligand for syndecans, and syndecan-2 is highly expressed in blood vessels. In this study, we prepared AG73 peptide-modified BLs (AG73-BLs) and assessed their specific attachment and ultrasound imaging ability for blood vessels in vitro and in vivo. First, we assessed the specific attachment of AG73-BLs in vitro, using flow cytometry and microscopy. AG73-BLs showed specific attachment compared with non-labeled or control peptide-modified BLs. Next, we examined ultrasound imaging in tumor-bearing mice. When BLs were administered, contrast imaging of AG73-BLs was sustainable for up to 4 min, while contrast imaging of non-labeled BLs was not observed. Thus, it is suggested that AG73-BLs may become useful ultrasound contrast agents in the clinic for diagnosis based on ultrasound imaging. (C) 2012 Elsevier Ltd. All rights reserved.