Photoacoustic Tomography Detects Early Vessel Regression and Normalization During Ovarian Tumor Response to the Antiangiogenic Therapy Trebananib

J Nucl Med. 2015 Dec;56(12):1942-7. doi: 10.2967/jnumed.115.160002. Epub 2015 Aug 27.

Abstract

The primary aim of this study was to assess the potential of in vivo photoacoustic tomography for direct functional measurement of ovarian tumor response to antiangiogenic therapy.

Methods: In vivo studies were performed with institutional animal care and use committee approval. We used an orthotopic mouse model of ovarian cancer treated with trebananib (n = 9) or vehicle (n = 9). Tumor-bearing mice were randomized into trebananib or vehicle groups at day 10 and dosed on days 12, 15, and 18 after implantation. Photoacoustic tomography and blood draws were performed at day 10 and then 24 h after each drug dose. Tumors were excised for histopathology after the final studies on day 19. Data analysis to test for statistical significance was performed blinded.

Results: Blockade of angiopoietin signaling using trebananib resulted in reduced total hemoglobin-weighted photoacoustic signal (n = 9, P = 0.01) and increased oxyhemoglobin-weighted photoacoustic signal (n = 9, P < 0.01). The latter observation indicated normalization of the residual tumor vessels, which was also implied by low levels of angiopoietin 1 in serum biomarker profiling (0.76 ± 0.12 ng/mL). These noninvasive measures reflected a 30% reduction in microvessel density and increased vessel maturation in ex vivo sections.

Conclusion: Photoacoustic tomography is able to evaluate both vessel regression and normalization in response to trebananib. Noninvasive imaging data were supported by modulation of serum markers in vitro and ex vivo histopathology.

Keywords: angiogenesis; angiopoietin; ovarian cancer; photoacoustics.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / therapeutic use*
  • Angiopoietin-1 / blood
  • Animals
  • Blood Vessels / pathology*
  • Cell Line, Tumor
  • Female
  • Hemoglobins / metabolism
  • Humans
  • Image Processing, Computer-Assisted
  • Luminescence
  • Mice
  • Ovarian Neoplasms / blood supply
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / pathology*
  • Photoacoustic Techniques / instrumentation
  • Photoacoustic Techniques / methods*
  • Recombinant Fusion Proteins / therapeutic use*
  • Regional Blood Flow / drug effects

Substances

  • Angiogenesis Inhibitors
  • Angiopoietin-1
  • Hemoglobins
  • Recombinant Fusion Proteins
  • trebananib