Pharmacodynamics of streptavidin-coated cyanoacrylate microbubbles designed for molecular ultrasound imaging.
OBJECTIVE
To assess the pharmacodynamic behavior of cyanoacrylate, streptavidin-coated microbubbles (MBs) and to investigate their suitability for molecular ultrasound imaging.


METHODS
Biodistribution of MBs was analyzed in tumor-bearing mice using gamma-counting, immunohistochemistry, flow cytometry, and ultrasound. Further, vascular endothelial growth factor receptor 2-antibody coupled MBs were used to image tumor neovasculature.


RESULTS
After 1 minute >90% of MBs were cleared from the blood and pooled in the lungs, liver, and spleen. Subsequently, within 1 hour a decent reincrease of MB-concentration was observed in the blood. The remaining MBs were removed by liver and spleen macrophages. About 30% of the phagocytosed MBs were intact after 48 hours. Shell fragments were found in the kidneys only. No relevant MB-accumulation was observed in tumors. In contrast, vascular endothelial growth factor receptor 2-specific MBs accumulated significantly within the tumor vasculature (P < 0.05).


CONCLUSIONS
The pharmacokinetic behavior of streptavidin-coated cyanoacrylate MBs has been studied. In this context, the low amount of MBs in tumors after >5 minutes is beneficial for specific targeting of angiogenesis.
Palmowski
Moritz
M
Department of Diagnostic Radiology, Ruprecht-Karls University, Heidelberg, Germany.
Morgenstern
Bernd
B
Hauff
Peter
P
Reinhardt
Michael
M
Huppert
Jochen
J
Maurer
Mathias
M
Woenne
Eva C
EC
Doerk
Sebastian
S
Ladewig
Gesa
G
Jenne
Juergen W
JW
Delorme
Stefan
S
Grenacher
Lars
L
Hallscheidt
Peter
P
Kauffmann
Guenter W
GW
Semmler
Wolfhard
W
Kiessling
Fabian
F
D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000000981:diagnostic imaging* / Q000378:metabolism*; D020099:Coated Materials, Biocompatible / Q000737:chemistry; D003287:Contrast Media / Q000493:pharmacokinetics*; D003487:Cyanoacrylates / Q000737:chemistry*; D008657:Metabolic Clearance Rate; D051379:Mice; D008819:Mice, Nude; D045423:Microbubbles; D009928:Organ Specificity; D019809:Streptavidin / Q000737:chemistry / Q000493:pharmacokinetics*; D014018:Tissue Distribution; D014463:Ultrasonography
D020099:Coated Materials, Biocompatible; D003287:Contrast Media; D003487:Cyanoacrylates; D019809:Streptavidin