Aloma L. D'Souza MS, PhD, Abstract Co-Author: Nothing to Disclose

Jeffrey Tseng MD, Abstract Co-Author: Nothing to Disclose

Jarrett Rosenberg PhD, Abstract Co-Author: Nothing to Disclose

Kim R. Butts-Pauly PhD, Abstract Co-Author: Nothing to Disclose

Sanjiv S. Gambhir MD, PhD, Abstract Co-Author: Board of Directors, Lumera Corporation Stockholder, Lumera Corporation Stockholder, Pfizer Inc Consultant, Spectrum Dynamics Ltd Stockholder, Spectrum Dynamics Ltd Grant, Johnson & Johnson Committee member, Amgen Inc Scientific Advisory Board, Novartis AG Scientific Advisory Board, Siemens AG Royalties, Reed Elsevier Scientific Advisory Board, Genentech, Inc Scientific Advisory Board, General Electric Company Grant, General Electric Company Research collaboration, GlaxoSmithKline plc Scientific Advisory Board, GlaxoSmithKline plc Scientific Advisory Board, Intronn Inc Research collaboration, Intronn Inc Grant, Intronn Inc Scientific Advisory Board, Lumen Therapeutics Consultant, MediGene AG Scientific Advisory Board, MediGene AG Consultant, Millennium Pharmaceuticals, Inc Research collaboration, Pfizer Inc Grant, Pfizer Inc Consultant, Koninklijke Philips Electronics NV Scientific Advisory Board, Koninklijke Philips Electronics NV Consultant, Pathwork Diagnostics Grant, Bayer AG Speaker, Siemens AG Scientific Advisory Board, Varian Medical Systems, Inc Scientific Advisory Board, VisualSonics Inc

Gary M. Glazer MD, Presenter: Consultant, Theranos, Inc Grant, General Electric Company Grant, Siemens AG

Low frequency ultrasound is known to compromise the permeability of cell membranes; we hypothesize and prove that this bioeffect of ultrasound can be used to release multiple biomarkers into the extracellular milieu. The release of biomarkers into circulation could lead to the earlier detection of cancer and identification of unknown incidental lesions.

Cancer cell lines (colon-LS174T; prostate-LNCaP) that produce biomarkers (CEA, CA19-9; PSA) were exposed to 1 MHz ultrasound in culture using various intensities and time. Subcutaneous tumors (>0.3cm3) of LS174T in mice (n=7 per group; n=28 total) were also sonicated directly over the tumors. Controls were sonicated on non-tumor bearing regions. The biomarkers were detected in culture media or murine blood samples, pre and post-ultrasound application, using an enzyme-linked immunosorbant assay.

Application of 1 MHz ultrasound pulses to cultured LS174T cells at various intensities was shown to amplify the CEA released into the media. Treatment of the cells (n=4) at a low intensity of 0.3 W/cm2 at 1 MHz and 10% duty cycle, showed an increase in release of both biomarkers CEA and CA 19-9 with time (0, 10, 30 min; p<0.05). The prostate cancer cell line LNCaP also showed substantial increases of PSA released in culture media both with an increase in intensity as well as with time. Subcutaneous tumors of LS174T showed a significant increase in CEA levels released post sonication at 2 W/cm2; 50 % duty cycle for 6 min (p<0.03), compared to the controls.

Increases in biomarker release were observed when ultrasound was directly applied to cells or tumors in living mice. We have demonstrated a novel method to amplify and localize multiple biomarkers using ultrasound. This provides a new way for Radiology and medical imaging to become involved in personalized medicine by using image-guided ultrasound to perturb lesions and release biomarkers from them. This has implications in both diagnosis and monitoring of therapy and points towards the ultimate use of focused ultrasound to amplify biomarker release in humans.

We have developed a new method, using ultrasound to amplify and localize biomarkers signals, which brings radiology into the realm of personalized medicine.

D'Souza, A, Tseng, J, Rosenberg, J, Butts-Pauly, K, Gambhir, S, Glazer, G, Low-Frequency Ultrasound Amplifies the Release of Multiple Tumor Biomarkers in Living Subjects.  Radiological Society of North America 2010 Scientific Assembly and Annual Meeting, November 28 - December 3, 2010 ,Chicago IL. http://archive.rsna.org/2010/9007743.html