Abstract 5114: Multispectral optoacoustic tomography (MSOT) as a novel approach for dynamic, noninvasive assessment of tumor therapy response and chronic inflammation
Authors: Driessen Wouter H. P. , Burton Neal , Schwöppe Christian , Berd Wolfgang E. , Weinhage Toni , Varga Georg , Geyer Christiane 
Published: August 2015

Biomedical imaging has offered a dramatic leap forward in cancer research by enabling non-invasive assessment of tumor biology in its native environment. Multiple modalities are currently utilized for this purpose, including molecular (e.g. PET, SPECT, optical imaging), functional (e.g. Doppler ultrasound) or anatomical (e.g. ultrasound, MRI, CT) endpoints. However, integrated multi-modality imaging can be impractical due to cost or infrastructure requirements, while co-registration of sequential imaging sessions can pose technical challenges. A single modality that offers anatomical, functional and molecular contrast could therefore provide the next leap forward in cancer research.

Multispectral Optoacoustic Imaging (MSOT) is an emerging modality that combines ultrasound resolution of 150 μm and acquisition times of a few microseconds with optical contrast in the near infrared (NIR) spectral region. Multispectral imaging allows the localization of injected targeted fluorophores with NIR absorbance to offer molecular contrast, while visualization of endogenous contrast such as deoxy-/oxy-hemoglobin or melanin offers both functional and anatomical information. A core imaging rate of 10 images/second allows the acquisition of a multispectral image within a second or even less.

In the present work, MSOT was used to track the fate of injected monocytes, labeled with an NIR chromophore, in a model of dss-induced colitis. Monocyte distribution in lymphoid organs (e.g. spleen) and chronic sites of inflammation, often a prerequisite for tumor development, in the gut was monitored over a 48 hour period. The axial image plane enables the discrimination of signal origin throughout the entire depth of the mouse, while 3D renderings of axial image stacks allow visualization of monocyte distribution throughout the abdominal region.

The functional response to an injection of a vascular disrupting agent in the HT1090 fibrosarcoma model was assessed by MSOT-mediated differentiation of oxygenated and deoxygenated hemoglobin signals. Truncated tissue factor (tTF) fused to an NGR-peptide (tTF-NGR) targets CD13, which is overexpressed in tumor endothelial cells. After binding, it is known to cause vascular disruption, blood pooling and vessel occlusions within the tumor vasculature. These processes were associated with an increase in MSOT-associated deoxyhemoblin signal in the tumor.

In summary, MSOT offers an imaging modality that can provide anatomical, functional, molecular and kinetic information at high temporal and spatial resolution. When combined with (molecular) imaging agents that possess appropriate targeting properties, this modality can be leveraged for new biomarker imaging approaches in cancer research.

Citation Format: Wouter H. P. Driessen, Neal Burton, Christian Schwöppe, Wolfgang E. Berd, Toni Weinhage, Georg Varga, Christiane Geyer. Multispectral optoacoustic tomography (MSOT) as a novel approach for dynamic, noninvasive assessment of tumor therapy response and chronic inflammation. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5114. doi:10.1158/1538-7445.AM2015-5114