In vivo imaging of microenvironmental and anti-PD-L1-mediated dynamics in cancer using S100A8/S100A9 as an imaging biomarker

Purpose: As a promotor of tumor invasion and tumor microenvironment (TME) formation, the protein complex S100A8/S100A9 is associated with poor prognosis. Our aim was to further evaluate its origin and regulatory effects, and to establish an imaging biomarker for TME activity. Methods: S100A9−/−cells (ko) were created from syngeneic murine breast cancer 4T1 (high malignancy) and 67NR (low malignancy) wildtype (wt) cell lines and implanted into either female BALB/c wildtype or S100A9−/− mice (n = 10 each). Anti-S100A9-Cy5.5-targeted fluorescence reflectance imaging was performed at 0 h and 24 h after injection. Potential early changes of S100A9-presence under immune checkpoint inhibition (anti-PD-L1, n = 7 vs. rat IgG2b as isotype control, n = 3) were evaluated. Results: In S100A9−/−mice contrast-to-noise-ratios were significantly reduced for wt and S100A9−/−tumors. No significant differences were detected for 4T1 ko and 67NR ko cells as compared to wildtype cells. Under anti-PD-L1 treatment S100A9 presence significantly decreased compared with the control group. Conclusion: Our results confirm a secretion of S100A8/S100A9 by the TME, while tumor cells do not apparently release the protein. Under immune checkpoint inhibition S100A9-imaging reports an early decrease of TME activity. Therefore, S100A9-specific imaging may serve as an imaging biomarker for TME formation and activity

Neue Kupplungsreaktionen mit (Butadien)zirconocen-Komplexen

Die Kupplungsreaktion von (Butadien)zirconocen mit Elektrophilen ist eine seit mehreren Jahren bekannte Reaktion. In der vorliegenden Arbeit konnte diese Reaktion auch erstmalig auf Imine angewendet werden, woraus die Bildung von metallacyclischen Komplexen mit einer pi-allylisch gebundenen Alkenyl-Einheit resultiert. Durch Reaktion mit etablierten Kationen-Bildnern wie z.B. Tris(penta- fluorphenyl)boran konnten aus den so erhaltenen Komplexen kationische Systeme generiert werden, die sich als aktiv bei der homogen katalysierten Olefinpolymerisation erwiesen haben. In einem zweiten Teil der Arbeit konnten durch die Umsetzung von Alkyl- Zirconocenverbindungen mit N-terminal geschützten Aminosäuren metall- organische Komplexe erhalten werden, die in Lösung ein ausgeprägtes Aggregationsverhalten zeigen. Kationen solcher Systeme können ebenfalls erhalten werden; in Lösung stabilisieren sie sich wie die neutralen Verbindungen durch Zusammenlagerung, z.B. zu Dimeren

Molecular imaging of integrins in oncology

Carsten Höltke,1 Andreas Faust2 1Department of Clinical Radiology, University Hospital Münster, and 2European Institute for Molecular Imaging, University of Münster, Münster, Germany Abstract: Integrins are a class of heterodimeric cell surface receptors with a variety of essential contributions to cell–cell and cell–extracellular matrix interactions. In particular, integrin αvβ3 plays an important role in the regulation of normal and tumor cell migration and survival, as well as in tumor angiogenesis and metastasis. Its overexpression has been proved for a number of malignancies, and the level of αvβ3 expression has been recognized as a potential surrogate marker of angiogenic activity. Therefore, αvβ3 represents an important target structure in noninvasive cancer diagnosis and the evaluation of antiangiogenic therapies. One common feature of many integrins is high-affinity binding to proteins containing an Arg-Gly-Asp (RGD) peptide motif, which can be found in their endogenous ligands, for example, fibronectin, vitronectin, and fibrinogen. Consequently, not only small synthetic peptides containing the RGD motif but also peptidomimetic structures based on RGD have been designed, and appropriate labeling strategies utilized them for molecular imaging approaches. This review focuses on recent advances of integrin molecular imaging in cancer diagnosis. First, clinical applications are highlighted, and then experimental approaches in preclinical research and multimodal setups are discussed. Keywords: integrins, angiogenesis, RGD, cancer diagnostic

Optoacoustic properties of Doxorubicin - A pilot study.

Doxorubicin (DOX) is a widely used chemotherapeutic anticancer drug. Its intrinsic fluorescence properties enable investigation of tumor response, drug distribution and metabolism. First phantom studies in vitro showed optoacoustic property of DOX. We therefore aimed to further investigate the optoacoustic properties of DOX in biological tissue in order to explore its potential as theranostic agent. We analysed doxorubicin hydrochloride (Dox center dot HCl) and liposomal encapsulated doxorubicin hydrochloride (Dox center dot Lipo), two common drugs for anticancer treatment in clinical medicine. Optoacoustic measurements revealed a strong signal of both doxorubicin substrates at 488 nm excitation wavelength. Post mortem analysis of intra-tumoral injections of DOX revealed a detectable optoacoustic signal even at three days after the injection. We thereby demonstrate the general feasibility of doxorubicin detection in biological tissue by means of optoacoustic tomography, which could be applied for high resolution imaging at mesoscopic depths dictated by effective penetration of visible light into the biological tissues