Molecular imaging of thrombus with microbubbles targeted to alphavbeta3-integrin using an agarose flow chamber model / 南方医科大学学报

<p><b>OBJECTIVE</b>To assess the binding ability of microbubbles targeted to alphavbeta3-integrin (MBp) for thrombus-targeted contrast-enhanced ultrasound.</p><p><b>METHODS</b>Targeted microbubbles were prepared by conjugating the monoclonal antibody against alphavbeta3-integrin to lipid shell of the microbubble via the avidin-biotin bridges. Equivalent isotype control microbubbles (MB) or targeted ultrasound microbubbles (MBp) were randomly added into the flow chamber. After a 30-min incubation with the thrombus fixed in an agarose flow chamber model, the thrombus was washed with a continuous flow of PBS solution (15 cm/s) for 2, 4, 6, 8 and 10 min, followed by thrombus imaging using contrast-enhanced ultrasound and measurement of the video intensity (VI) values of the images.</p><p><b>RESULTS</b>The VI of the thrombus in MBp group was reduced by 28%-66%, while that in control MB group was decreased by 87%-94%, and the VI values of the thrombus group were significantly greater in former group at each of the time points (P<0.05).</p><p><b>CONCLUSION</b>MBP has good targeting ability to the thrombus with resistance to the shear stress after adhesion to the thrombus. In vitro evaluation of the thrombus-binding capability of the targeted microbubble (MBp) by simulating the shear stress in vivo can be helpful for predicting the in vivo effects of ultrasonic molecular imaging using MBp.</p>

Evaluation of tumor angiogenesis using microbubbles conjugated with RGD peptides and contrast enhanced ultrasound / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To assess the feasibility of usage of microbubbles conjugated with RGD peptides and contrast enhanced ultrasound (CEU) in detection of tumor angiogenesis.</p><p><b>METHODS</b>Lipid microbubbles (MB) were prepared, and the RGD peptides were covalently conjugated to the lipid shell of MB (MB(RGD)). Six nude mice with tumor created by dorsal inoculation of HepG2 tumor cells were used as the test group. Six nude mice without tumor were served as the control group. 10 minutes after bolus injection of MB and MB(RGD) randomly (30 min interval) via a tail vein catheter, CEU was performed on the tumors of the test group and the thigh skeletal muscles of control group. The video intensity (VI) of tumors and the skeletal muscles were measured. The tumors and the skeletal muscles were harvested for immunohistochemical examination.</p><p><b>RESULTS</b>Only a slight contrast enhancement of the tumor was seen with MB, and the VI was 5.33 ± 1.71. While a remarkable enhancement of the tumor was observed after injection of MB(RGD). The VI was up to 17.03 ± 3.58, 3.18 folds higher as compared with that obtained by injection of MB (P < 0.05). As expected, there were no obvious contrast enhancement of the skeletal muscles with both MB(RGD) and MB. There was a high expression of αvβ3-integrin in tumor neovascular endothelium, however, no apparent expression of αvβ3-integrin was observed in the skeletal muscle vascular endothelium.</p><p><b>CONCLUSION</b>CEU with MB(RGD) can be used to effectively evaluate the angiogenesis of tumors, and it may greatly contribute to the early judgement of the nature of tumor.</p>