Scanning Acoustic Microscopy-A Novel Noninvasive Method to Determine Tumor Interstitial Fluid Pressure in a Xenograft Tumor Model.
Elevated tumor interstitial fluid pressure (TIFP) is a prominent feature of solid tumors and hampers the transmigration of therapeutic macromolecules, for example, large monoclonal antibodies, from tumor-supplying vessels into the tumor interstitium. TIFP values of up to 40 mm Hg have been measured in experimental solid tumors using two conventional invasive techniques: the wick-in-needle and the micropuncture technique. We propose a novel noninvasive method of determining TIFP via ultrasonic investigation with scanning acoustic microscopy at 30-MHz frequency. In our experimental setup, we observed for the impedance fluctuations in the outer tumor hull of A431-vulva carcinoma-derived tumor xenograft mice. The gain dependence of signal strength was quantified, and the relaxation of tissue was calibrated with simultaneous hydrostatic pressure measurements. Signal patterns from the acoustical images were translated into TIFP curves, and a putative saturation effect was found for tumor pressures larger than 3 mm Hg. This is the first noninvasive approach to determine TIFP values in tumors. This technique can provide a potentially promising noninvasive assessment of TIFP and, therefore, can be used to determine the TIFP before treatment approach as well to measure therapeutic efficacy highlighted by lowered TFP values.
Department of Dermatology, Venereology and Allergology, Goethe University Frankfurt, 60590, Frankfurt am Main, Germany. Electronic address: matthias.hofmann@em.uni-frankfurt.de.
Matthias
M
Hofmann
Department of Dermatology, Venereology and Allergology, Goethe University Frankfurt, 60590, Frankfurt am Main, Germany.
Ralph
R
Pflanzer
Dept. of Physics and Technology, University of Tromsø, 9037, Tromsø, Norway; Institute for Cell Biology and Neurosciences, Goethe University Frankfurt, 60439, Frankfurt am Main, Germany.
Anowarul
A
Habib
Department of Civil Engineering, Indian Institute of Technology, Guwahati, India.
Amit
A
Shelke
Institute for Cell Biology and Neurosciences, Goethe University Frankfurt, 60439, Frankfurt am Main, Germany.
Jürgen
J
Bereiter-Hahn
Department of Dermatology, Venereology and Allergology, Goethe University Frankfurt, 60590, Frankfurt am Main, Germany.
August
A
Bernd
Department of Dermatology, Venereology and Allergology, Goethe University Frankfurt, 60590, Frankfurt am Main, Germany.
Roland
R
Kaufmann
Department of Oral, Craniomaxillofacial and Facial Plastic Surgery, Goethe University Frankfurt, 60590, Frankfurt am Main, Germany.
Robert
R
Sader
Department of Dermatology, Venereology and Allergology, Goethe University Frankfurt, 60590, Frankfurt am Main, Germany.
Stefan
S
Kippenberger