Imaging with Bubbles…Next Generation Tool for Molecular Imaging?
By Melissa Yin, Scientific Applications Specialist
Since their discovery in the 1970s, contrast enhanced ultrasound imaging (CEUS) using microbubbles (micron sized gas bubbles injected intravenously to enhance the signal from blood) have come a long way. From agitated saline solutions to now commercially available agents made with biocompatible materials and low blood solubility gases1; they are now used clinically in more than 70 countries. Yet, the recent 2016 FDA approval of Bracco’s Lumason for its use in liver lesion detection for both adults and children, marks a milestone for microbubble imaging, making it the first approved ultrasound contrast agent (UCA) for use in applications outside of cardiology in the United States2. Paving the way for increased adoption and expanded clinical use of microbubbles in abdominal and pelvic imaging.
An extension of CEUS is the introduction of molecularly targeted UCAs – microbubbles decorated with targeting ligands – used to evaluate changes in expression levels of key vascular endothelial biomarkers under pathological conditions. Although still in its initial phase of clinical translation, recent 2017 publications from Willmann et al3 at Stanford, and Smeenge et al4 from the Netherlands have shown first-in-human results of ultrasound molecular imaging (USMI) in breast, ovarian and prostate cancer. Both studies used BR55, a clinical grade microbubble targeted to vascular endothelial growth factor receptor 2 (VEFGR2), to evaluate its safety and feasibility for cancer detection. When imaging results were compared to gold standard histopathology. Willmann et al found that 77% of malignant ovarian and 93% of malignant breast lesions were detected by BR55 targeted UCAs. Whereas a 68% detection rate was observed by Smeenge et al for malignant prostate lesions. No safety concerns were indicated in both studies, opening the door for USMI to be used as a diagnostic tool for cancer evaluation.
Although USMI has made its first step toward clinical use in radiology, exploration of clinical applications related the use of molecularly targeted UCAs is not limited to cancer detection. An abundant amount of preclinical literature have surfaced in the last decade; investigating the use of USMI in various disease processes such as inflammation, ischemia reperfusion and atherosclerosis5. The agent used in many of these studies was Target-Ready Vevo®MicroMarker 6-10. With streptavidin incorporated into its phospholipid shell, these targeted microbubbles provides the flexibility of attaching any biotinylated antibody of choice, allowing for the assessment of novel applications.
As an imaging modality, ultrasound is known to provide high spatial and temporal resolution at relatively low costs, and free of ionizing radiation. With the approval of Lumason’s use in liver imaging and first-in-human results of BR55 showing clinical feasibility and safety, the era of USMI as a next generation tool for disease diagnosis and monitoring, may not be so far away.
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