Release of Cell-free MicroRNA Tumor Biomarkers into the Blood Circulation with Pulsed Focused Ultrasound: A Noninvasive, Anatomically Localized, Molecular Liquid Biopsy

• DOI: 10.1148/radiol.2016160024
• Publication Date: 2016-11-01T15:08:55Z
• Authors: John R. Chevillet; Tatiana D. Khokhlova; Maria D. Giraldez; George R. Schade; Frank Starr; Yak-Nam Wang; Emily N. Gallichotte; Kai Wang; Joo Ha Hwang; Muneesh Tewari
• Keywords: Liquid biopsy; Blood circulation; Cell-free fetal DNA; Focused Ultrasound

Purpose To compare the abilities of three pulsed focused ultrasound regimes (that cause tissue liquefaction, permeabilization, or mild heating) to release tumor-derived microRNA into circulation in vivo and evaluate dynamics. Materials Methods All rat experiments were approved by University Washington Institutional Animal Care Use Committee. Reverse-transcription quantitative polymerase chain reaction array profiling was used identify candidate biomarkers a solid tumor cell line. Rats subcutaneously grafted with these cells randomly assigned among treatment groups: (a) local liquefaction via boiling histotripsy, (b) permeabilization inertial cavitation, (c) (<10°C) heating tissue, as well sham-treated control group. Blood specimens drawn immediately prior serially over 24 hours afterward. Plasma quantified reverse-transcription reaction, statistical significance determined one-way analysis variance (Kruskal-Wallis Friedman tests), followed Dunn multiple-comparisons test. Results After cavitation treatments (but not heating), plasma quantities increased significantly (P value range, <.0001 .04) relative controls. A threefold 32-fold increase occurred within 15 minutes after initiation treatment, increases persisted for 3 hours. Histologic examination confirmed complete targeted area addition areas petechial hemorrhage disruption means cavitation-based treatment. Conclusion Mechanical ultrasound–induced bubble activity abundance rapidly © RSNA, 2016 Online supplemental material is available this article.