BR55: A Lipopeptide-Based VEGFR2-Targeted Ultrasound Contrast Agent for Molecular Imaging of Angiogenesis

Pochon, Sibylle; Tardy, Isabelle; Bussat, Philippe; Bettinger, Thierry; Brochot, Jean; Wronski, Mathew von; Passantino, Lisa; Schneider, Michel

doi:10.1097/rli.0b013e3181c5927c

Cited by 239 publications

(188 citation statements)

References 32 publications

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“…The most successful of these is the BR55, which targets VEGFR and has been reported in tumor diagnosis and evaluations of anti-vascular therapy. 34,35 In the ultrasound molecular imaging of tumor parenchyma, targeted ultrasound microbubbles at the micron scale cannot penetrate tumor blood vessels to enter tumor tissues; therefore, there are fewer relevant studies on the direct specific binding between ultrasound microbubbles and tumor cells to achieve targeted imaging.…”

mentioning

confidence: 99%

Diagnosis of prostate cancer using anti-PSMA aptamer A10-3.2-oriented lipid nanobubbles

Fan

Guo

Wang

et al. 2016

IJN

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In this study, the lipid targeted nanobubble carrying the A10-3.2 aptamer against prostate specific membrane antigen was fabricated, and its effect in the ultrasound imaging of prostate cancer was investigated. Materials including 2-dipalmitoyl-sn-glycero-3-phosphocholine, 1,2-dipalmitoyl-sn-glycero-3-phosphatidic acid, 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine, 1,2-dipalmitoyl-sn-glycero-3-phosphoglycerol, carboxyl-modified 1,2-distearoyl-sn-glycero-3-phosphoethanolamine, and polyethyleneglycol-2000 were for mechanical oscillation, and nanobubbles were obtained through the centrifugal flotation method. After mice were injected with nanobubbles, abdominal color Doppler blood flow imaging significantly improved. Through left ventricular perfusion with normal saline to empty the circulating nanobubbles, nanobubbles still existed in tumor tissue sections, which demonstrated that nanobubbles could enter tissue spaces via the permeability and retention effect. Fluorinated A10-3.2 aptamers obtained by chemical synthesis had good specificity for PSMA-positive cells, and were linked with carboxyl-modified 1,2-distearoyl-sn-glycero-3-phosphoethanolamine lipid molecules from the outer shell of nanobubbles via amide reaction to construct targeted nanobubbles. Gel electrophoresis and immunofluorescence confirmed that targeted nanobubbles were fabricated successfully. Next, targeted nanobubbles could bind with PSMA-positive cells (C4-2 cells), while not with PSMA-negative cells (PC-3 cells), using in vitro binding experiments and flow cytometry at the cellular level. Finally, C4-2 and PC-3 xenografts in mice were used to observe changes in parameters of targeted and non-targeted nanobubbles in the contrast-enhanced ultrasound mode, and the distribution of Cy5.5-labeled targeted nanobubbles in fluorescent imaging of live small animals. Comparison of ultrasound indicators between targeted and non-targeted nanobubbles in C4-2 xenografts showed that they had similar peak times ( P >0.05), while the peak intensity, half time of peak intensity, and area under the curve of ½ peak intensity were significantly different ( P <0.05). In PC-3 xenografts, there were no differences in these four indicators. Fluorescent imaging indicated that targeted nanobubbles had an aggregation ability in C4-2 xenograft tumors. In conclusion, targeted nanobubbles carrying the anti-PSMA A10-3.2 aptamer have a targeted imaging effect in prostate cancer.

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mentioning

confidence: 99%

Diagnosis of prostate cancer using anti-PSMA aptamer A10-3.2-oriented lipid nanobubbles

Fan

Guo

Wang

et al. 2016

IJN

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“…For example, human vascular endothelial growth factor receptor 2-targeted lipopeptide can be incorporated into the microbubble shell to create a molecularly targeted clinical ultrasound contrast agent. 108 If chemotherapeutics can be loaded into this ultrasound contrast agent, it will achieve the dual function of theranostics, ie, monitoring of tumor angiogenesis and delivering targeted therapy.…”

Section: Theranosticsmentioning

confidence: 99%

Potential and problems in ultrasound-responsive drug delivery systems

Zhao¹,

Du²,

Lu³

et al. 2013

IJN

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Abstract:Ultrasound is an important local stimulus for triggering drug release at the target tissue. Ultrasound-responsive drug delivery systems (URDDS) have become an important research focus in targeted therapy. URDDS include many different formulations, such as microbubbles, nanobubbles, nanodroplets, liposomes, emulsions, and micelles. Drugs that can be loaded into URDDS include small molecules, biomacromolecules, and inorganic substances. Fields of clinical application include anticancer therapy, treatment of ischemic myocardium, induction of an immune response, cartilage tissue engineering, transdermal drug delivery, treatment of Huntington's disease, thrombolysis, and disruption of the blood-brain barrier. This review focuses on recent advances in URDDS, and discusses their formulations, clinical application, and problems, as well as a perspective on their potential use in the future.

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“…These binding ligands can either be coupled to the microbubbles using non-covalent attachment, or chemical conjugation (Klibanov 2005), or they can be integrated into the microbubble shell directly during the production process or after manufacturing (Pochon, Tardy et al 2010;Pysz, Foygel et al 2010). …”

Section: Dynamic Contrast-enhanced Ultrasoundmentioning

confidence: 99%

Molecular Imaging of Tumor Angiogenesis

McDermott¹,

Guimaraes²

2012

Molecular Imaging

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BR55: A Lipopeptide-Based VEGFR2-Targeted Ultrasound Contrast Agent for Molecular Imaging of Angiogenesis

Abstract: VEGFR2-targeted ultrasound contrast agents such as BR55 will likely prove useful in human for the early detection of tumors as well as for the assessment of response to specific treatments.

Cited by 239 publications

References 32 publications

Diagnosis of prostate cancer using anti-PSMA aptamer A10-3.2-oriented lipid nanobubbles

Diagnosis of prostate cancer using anti-PSMA aptamer A10-3.2-oriented lipid nanobubbles

Potential and problems in ultrasound-responsive drug delivery systems

Molecular Imaging of Tumor Angiogenesis

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