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Low-Dose Molecular Ultrasound Imaging with E-Selectin-Targeted PBCA Microbubbles.

Abstract：

PURPOSE:Our objective was to determine the lowest diagnostically effective dose for E-selectin-targeted poly n-butyl cyanoacrylate (PBCA)-shelled microbubbles and to apply it to monitor antiangiogenic therapy effects. PROCEDURES:PBCA-shelled microbubbles (MBs) coupled to an E-selectin-specific peptide were applied in mice carrying MLS or A431 carcinoma xenografts scaling down the MB dosage to the lowest level where binding could be examined with a 18-MHz small animal ultrasound transducer. Differences in E-selectin expression in the two carcinoma xenografts were confirmed by enzyme-linked immunosorbent assay (ELISA). In addition, MLS tumor-bearing mice under antiangiogenic therapy were monitored using E-selectin-targeted MBs at the lowest applicable dose. Therapy effects on tumor vascularization were verified by immunohistological analyses. RESULTS:The minimally required dosage was 7 × 10(7) MBs/kg body weight. This dosage was sufficient to enable E-selectin detection in high E-selectin-expressing MLS tumors, while low E-selectin-expressing A431 tumors required almost 2.5-fold higher doses. At the dose of 7 × 10(7) MBs/kg body weight, a decrease in E-selectin MB binding under antiangiogenic therapy could be assessed (being significant after 3 days of treatment; p < 0.0001), which was in line with the significant drop in E-selectin-positive area fractions that was found histologically (p < 0.05). CONCLUSIONS:Molecular ultrasound imaging with our E-selectin-targeted MB and therapy monitoring was possible down to a dose of 7 × 10(7) MBs/kg body weight (equates to 66 μg PBCA/kg and 4.6 mg PBCA/70 kg). Improvements in choice of targets, MB composition, and other MB detection methods may improve sensitivity and lead to reliable detection results of clinically transferrable MBs at even lower dosage levels.

journal_name

Mol Imaging Biol

journal_title

Molecular imaging and biology

authors

Spivak I,Rix A,Schmitz G,Fokong S,Iranzo O,Lederle W,Kiessling F

doi

10.1007/s11307-015-0894-9

subject

Has Abstract

pub_date

2016-04-01 00:00:00

pages

180-90

issue

eissn

1536-1632

issn

1860-2002

pii

10.1007/s11307-015-0894-9

journal_volume

pub_type

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Low-Dose Molecular Ultrasound Imaging with E-Selectin-Targeted PBCA Microbubbles.