Sonobiopsy of glioblastoma
Glioblastoma is an aggressive brain tumor that is usually diagnosed with a surgical biopsy. A group of researchers led by Hong Chen from Washington University in St. Louis has developed a non-invasive diagnostic method that could one day replace tissue biopsy with a simple blood test. The researchers tested the method on small and large animals and found a higher sensitivity for detecting and diagnosing brain tumors using a simple blood test.
The method, called sonobiopsy by the authors, consists in the effect of focused ultrasound on tumors located deep in the brain tissue, followed by the introduction of microbubbles into the blood. They move to the tissue to which the ultrasound is directed and pulsate, which temporarily safely "opens" the blood-brain barrier. At this point, tumor biomarkers, such as DNA, RNA and proteins, pass through the blood-brain barrier and enter the blood.
Chen and his group have been working on a liquid biopsy method using ultrasound for several years, first performing a feasibility study on mice, followed by a safety assessment study, and more recently another study on pigs. Blood-based liquid biopsy has already been used in people with cancer, but the use of this method in brain tumors has been limited due to the blood-brain barrier.
In studies on mouse models of glioblastoma, Chen's group found that the sonobiopsy method made it possible to detect the EGFRvIII gene in the blood, a mutant form of the epidermal growth factor receptor characteristic of this type of tumor. After sonobiopsy, the level of circulating tumor DNA EGFRvIII in plasma was 920 times higher than in the group of mice that underwent a liquid biopsy based on a blood sample. The detection of another circulating genetic marker of the tumor, a mutant form of telomerase reverse transcriptase – TERT C228T, was 10 times higher after sonobiopsy. The method improved diagnostic sensitivity from 7.14% to 64.71% for EGFRvIII and from 14.29% to 45.83% for TERT C228T. The group found no tissue damage in the tumor area of interest after sonobiopsy.
In pig models, sonobiopsy resulted in a 270-fold increase in circulating EGFRvIII tumor DNA and a nine-fold increase in circulating TERT tumor DNA. This improved diagnostic sensitivity from 28.57% to 100% for EGFRvIII and from 42.86% to 71.43% for TERT C228T. No significant tissue damage was found.
The study showed that sonobiopsy led to an increase in tumor-specific circulating DNA in plasma and improved the sensitivity of the diagnosis of two glioblastoma phenotypes, while not carrying significant risks for the animal. The integration of sonobiopsy with advanced blood analysis methods will provide minimally invasive, controlled and sensitive diagnosis of brain tumors.
Complementing neuroimaging and analysis of surgically obtained tissue, sonobiopsy can become an indispensable assistant for the treatment of brain tumors, significantly improving the diagnosis of glioblastoma, monitoring of treatment and detection of relapses. These opportunities can have an important impact on the entire process of providing medical care to cancer patients.
Article by C.P.Pacia et al. Sonobiopsy for minimally invasive, spatiotemporally-controlled, and sensitive detection of glioblastoma-derived circulating tumor DNA is published in the journal Theranostics.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on materials from Washington University in St. Louis: Noninvasive brain biopsy shows improved sensitivity in tumor detection.