Visualization of Tumor-Immune Interaction - Target-Specific Imaging of S100A8/A9 Reveals Pre-Metastatic Niche Establishment

• Published in: Theranostics 2017-01, Vol.7 (9), p.2392-2401
• Main Authors: Eisenblaetter, Michel, Flores-Borja, Fabian, Lee, Jae Jin, Wefers, Christina, Smith, Hannah, Hueting, Rebekka, Cooper, Margaret S, Blower, Philip J, Patel, Dominic, Rodriguez-Justo, Manuel, Milewicz, Hanna, Vogl, Thomas, Roth, Johannes, Tutt, Andrew, Schaeffter, Tobias, Ng, Tony
• Format: Article
• Language: English
• Subjects: Animals; Breast Neoplasms - secondary; Calgranulin A - analysis; Calgranulin B - analysis; Disease Models, Animal; Flow Cytometry; Lung Neoplasms - secondary; Mice, Inbred BALB C; Microscopy, Confocal; Neoplasm Metastasis - diagnostic imaging; Research Paper; Tomography, Emission-Computed, Single-Photon - methods
• ISSN: 1838-7640; 1838-7640
• DOI: 10.7150/thno.17138

Systemic cancer spread is preceded by the establishment of a permissive microenvironment in the target tissue of metastasis - the premetastatic niche. As crucial players in establishment of the pre-metastatic niche, myeloid derived suppressor cells (MDSC) release S100A8/A9, an exosomal protein that contributes to metastasis, angiogenesis, and immune suppression. We report the application of antibody-based single-photon emission computed tomography (SPECT) for detection of S100A8/A9 as an imaging marker for pre-metastatic tissue priming. A syngeneic model system for invasive breast cancer with (4T1.2) or without (67NR) the tendency to form lung metastasis was established in BALB/c mice. A SPECT-probe has been generated and tested for visualization of S100A9 release. Tumor-associated changes in numbers and fuction of immune cells in pre-metastatic tissue were evaluated by flow cytometry and confocal microscopy. S100A8/A9 imaging reflected MDSC abundance and the establishment of an immunosuppressive environment in pre-metastatic lung tissue (activity 4T1.2 vs. healthy control: 0.95 vs. 0.45 %ID; p