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Novel Targeted Contrast Agent for Ultrasound Molecular Imaging of αvβ3 Integrin
Author(s) -
Anderson Christopher R,
Rychak Joshua J,
Hu Xiaowen,
Ferrara Katherine
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.793.8
Subject(s) - contrast (vision) , integrin , molecular imaging , ultrasound imaging , ultrasound , medicine , radiology , computer science , biology , artificial intelligence , microbiology and biotechnology , receptor , in vivo
Ultrasound molecular imaging enables sensitive detection of molecular markers of tumor angiogenesis. We developed a microbubble (MB) ultrasound contrast agent targeted to αvβ3 integrins, which are overexpressed on the angiogenic endothelium. A cyclic RGD (cRGD) pentapeptide was covalently conjugated to PDP‐MB surfaces by disulfide exchange chemistry. FITC labeled cRGD peptides were reacted with MB surfaces and the cRGD load was quantified by plate fluorometry (~8.2 × 106 molecules/MB), and detected by flow cytometry and fluorescence microscopy. Adhesion of cRGD‐MB was demonstrated with in vitro flow adhesion assays. At 1 dynes/cm2, cRGD‐MB exhibited 5‐fold higher adhesion to immobilized recombinant αvβ3 integrin relative to non‐targeted MB and cRAD‐MB controls. Also, cRGD‐MB showed significantly greater adhesion to αvβ3 integrin expressing endothelial cells (bEnd.3) and adhesion was blocked with an anti‐αv monoclonal antibody. In a murine model of mammary carcinoma, cRGD‐MB, but not non‐targeted MB or cRAD‐MB, showed significantly enhanced contrast signals with a high tumor‐to‐background ratio. The accumulation of cRGD‐MB was blocked by pre‐administration with an anti‐αv blocking antibody. The results demonstrate the functionality of a novel microbubble contrast agent covalently coupled to an RGD peptide for ultrasound molecular imaging of αvβ3 integrin. Supported by NIH 1R43CA137913 to CRA.