@article{WernerKircherHiguchietal.2019,
  author    = {Werner, Rudolf A. and Kircher, Stefan and Higuchi, Takahiro and Kircher, Malte and Schirbel, Andreas and Wester, Hans-J{\"u}rgen and Buck, Andreas K. and Pomper, Martin G. and Rowe, Steven P. and Lapa, Constantin},
  title     = {CXCR4-directed imaging in solid tumors},
  series = {Frontiers in Oncology},
  volume    = {9},
  journal   = {Frontiers in Oncology},
  number    = {770},
  issn      = {2234-943X},
  doi       = {10.3389/fonc.2019.00770},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-195678},
  year      = {2019},
  abstract  = {Despite histological evidence in various solid tumor entities, available experience with CXCR4-directed diagnostics and endoradiotherapy mainly focuses on hematologic diseases. With the goal of expanding the application of CXCR4 theranostics to solid tumors, we aimed to elucidate the feasibility of CXCR4-targeted imaging in a variety of such neoplasms. Methods: Nineteen patients with newly diagnosed, treatment-na{\"i}ve solid tumors including pancreatic adenocarcinoma or neuroendocrine tumor, cholangiocarcinoma, hepatocellular carcinoma, renal cell carcinoma, ovarian cancer, and prostate cancer underwent [\(^{68}\)Ga]Pentixafor PET/CT. CXCR4-mediated uptake was assessed both visually and semi-quantitatively by evaluation of maximum standardized uptake values (SUV\(_{max}\)) of both primary tumors and metastases. With physiologic liver uptake as reference, tumor-to-background ratios (TBR) were calculated. [\(^{68}\)Ga]Pentixafor findings were further compared to immunohistochemistry and [\(^{18}\)F]FDG PET/CT. Results: On [\(^{68}\)Ga]Pentixafor PET/CT, 10/19 (52.6\%) primary tumors were visually detectable with a median SUVmax of 5.4 (range, 1.7-16.0) and a median TBR of 2.6 (range, 0.8-7.4), respectively. The highest level of radiotracer uptake was identified in a patient with cholangiocarcinoma (SUVmax, 16.0; TBR, 7.4). The relatively low uptake on [\(^{68}\)Ga]Pentixafor was also noted in metastases, exhibiting a median SUVmax of 4.5 (range, 2.3-8.8; TBR, 1.7; range, 1.0-4.1). A good correlation between uptake on [\(^{68}\)Ga]Pentixafor and histological derived CXCR4 expression was noted (R = 0.62, P < 0.05). In the 3 patients in whom [\(^{18}\)F]FDG PET/CT was available, [\(^{68}\)Ga]Pentixafor exhibited lower uptake in all lesions. Conclusions: In this cohort of newly diagnosed, treatment-na{\"i}ve patients with solid malignancies, CXCR4 expression as detected by [\(^{68}\)Ga]Pentixafor-PET/CT and immunohistochemistry was rather moderate. Thus, CXCR4-directed imaging may not play a major role in the management of solid tumors in the majority of patients.},
  language  = {en}
}
@article{SchuetzeRoehringVorlovaetal.2015,
  author    = {Sch{\"u}tze, Friedrich and R{\"o}hring, Florian and Vorlov{\´a}, Sandra and G{\"a}tzner, Sabine and Kuhn, Anja and Erg{\"u}n, S{\"u}leyman and Henke, Erik},
  title     = {Inhibition of lysyl oxidases improves drug diffusion and increases efficacy of cytotoxic treatment in 3D tumor models},
  series = {Scientific Reports},
  volume    = {5},
  journal   = {Scientific Reports},
  number    = {17576},
  doi       = {10.1038/srep17576},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-145109},
  year      = {2015},
  abstract  = {Tumors are characterized by a rigid, highly cross-linked extracellular matrix (ECM), which impedes homogeneous drug distribution and potentially protects malignant cells from exposure to therapeutics. Lysyl oxidases are major contributors to tissue stiffness and the elevated expression of these enzymes observed in most cancers might influence drug distribution and efficacy. We examined the effect of lysyl oxidases on drug distribution and efficacy in 3D in vitro assay systems. In our experiments elevated lysyl oxidase activity was responsible for reduced drug diffusion under hypoxic conditions and consequently impaired cytotoxicity of various chemotherapeutics. This effect was only observed in 3D settings but not in 2D-cell culture, confirming that lysyl oxidases affect drug efficacy by modification of the ECM and do not confer a direct desensitizing effect. Both drug diffusion and efficacy were strongly enhanced by inhibition of lysyl oxidases. The results from the in vitro experiments correlated with tumor drug distribution in vivo, and predicted response to therapeutics in murine tumor models. Our results demonstrate that lysyl oxidase activity modulates the physical barrier function of ECM for small molecule drugs influencing their therapeutic efficacy. Targeting this process has the potential to significantly enhance therapeutic efficacy in the treatment of malignant diseases.},
  language  = {en}
}