[Evaluation of tumor angiogenesis using microbubbles conjugated with RGD peptides and contrast enhanced ultrasound].
OBJECTIVE
To assess the feasibility of usage of microbubbles conjugated with RGD peptides and contrast enhanced ultrasound (CEU) in detection of tumor angiogenesis.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
Guang-quan
GQ
Hu
Li
L
Yang
Yun-bin
YB
Xiao
Jia-jia
JJ
Xie
Jue-fei
JF
Wu
Jing-jing
JJ
Cai
Jian
J
Liu
Wang-jun
WJ
Liao
Jian-ping
JP
Bin
D000818:Animals; D045744:Cell Line, Tumor; D003287:Contrast Media; D004730:Endothelium, Vascular / Q000000981:diagnostic imaging / Q000378:metabolism; D005260:Female; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D008113:Liver Neoplasms / Q000098:blood supply* / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008819:Mice, Nude; D045423:Microbubbles; D018482:Muscle, Skeletal / Q000098:blood supply; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D009842:Oligopeptides; D014465:Ultrasonics / Q000379:methods; D014463:Ultrasonography
D003287:Contrast Media; D039302:Integrin alphaVbeta3; D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid