TY - JOUR A1 - Hahn, Lukas A1 - Beudert, Matthias A1 - Gutmann, Marcus A1 - Keßler, Larissa A1 - Stahlhut, Philipp A1 - Fischer, Lena A1 - Karakaya, Emine A1 - Lorson, Thomas A1 - Thievessen, Ingo A1 - Detsch, Rainer A1 - Lühmann, Tessa A1 - Luxenhofer, Robert T1 - From Thermogelling Hydrogels toward Functional Bioinks: Controlled Modification and Cytocompatible Crosslinking JF - Macromolecular Bioscience N2 - Hydrogels are key components in bioink formulations to ensure printability and stability in biofabrication. In this study, a well-known Diels-Alder two-step post-polymerization modification approach is introduced into thermogelling diblock copolymers, comprising poly(2-methyl-2-oxazoline) and thermoresponsive poly(2-n-propyl-2-oxazine). The diblock copolymers are partially hydrolyzed and subsequently modified by acid/amine coupling with furan and maleimide moieties. While the thermogelling and shear-thinning properties allow excellent printability, trigger-less cell-friendly Diels-Alder click-chemistry yields long-term shape-fidelity. The introduced platform enables easy incorporation of cell-binding moieties (RGD-peptide) for cellular interaction. The hydrogel is functionalized with RGD-peptides using thiol-maleimide chemistry and cell proliferation as well as morphology of fibroblasts seeded on top of the hydrogels confirm the cell adhesion facilitated by the peptides. Finally, bioink formulations are tested for biocompatibility by incorporating fibroblasts homogenously inside the polymer solution pre-printing. After the printing and crosslinking process good cytocompatibility is confirmed. The established bioink system combines a two-step approach by physical precursor gelation followed by an additional chemical stabilization, offering a broad versatility for further biomechanical adaptation or bioresponsive peptide modification. KW - chemical crosslinking KW - biofabrication KW - bioprinting KW - hydrogels Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-257542 VL - 21 IS - 10 ER - TY - JOUR A1 - Hahn, Lukas A1 - Luxenhofer, Robert A1 - Helten, Holger A1 - Forster, Stefan A1 - Fritze, Lars A1 - Polzin, Lando A1 - Keßler, Larissa T1 - ABA Type Amphiphiles with Poly(2-benzhydryl-2-oxazine) Moieties: Synthesis, Characterization and Inverse Thermogelation JF - Macromolecular Chemistry and Physics N2 - Thermoresponsive polymers are frequently involved in the development of materials for various applications. Here, polymers containing poly(2- benzhydryl-2-oxazine) (pBhOzi) repeating units are described for the first time. The homopolymer pBhOzi and an ABA type amphiphile comprising two flanking hydrophilic A blocks of poly(2-methyl-2-oxazoline) (pMeOx) and the hydrophobic aromatic pBhOzi central B block (pMeOx-b-pBhOzi-b-pMeOx) are synthesized and the latter is shown to exhibit inverse thermogelling properties at concentrations of 20 wt.% in water. This behavior stands in contrast to a homologue ABA amphiphile consisting of a central poly(2-benzhydryl-2-oxazoline) block (pMeOx-b-pBhOx-b-pMeOx). No inverse thermogelling is observed with this polymer even at 25 wt.%. For 25 wt.% pMeOx-b-pBhOzi-b-pMeOx, a surprisingly high storage modulus of ≈22 kPa and high values for the yield and flow points of 480 Pa and 1.3 kPa are obtained. Exceeding the yield point, pronounced shear thinning is observed. Interestingly, only little difference between self-assemblies of pMeOx-b-pBhOzi-b-pMeOx and pMeOx-b-pBhOx-b-pMeOx is observed by dynamic light scattering while transmission electron microscopy images suggest that the micelles of pMeOx-b-pBhOzi-b-pMeOx interact through their hydrophilic coronas, which is probably decisive for the gel formation. Overall, this study introduces new building blocks for poly(2-oxazoline) and poly(2-oxazine)-based self-assemblies, but additional studies will be needed to unravel the exact mechanism. KW - inverse thermogels KW - physical hydrogels KW - poly(2-oxazine) KW - poly(2- oxazoline) KW - self-assembly Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-265124 VL - 222 IS - 17 ER - TY - JOUR A1 - Giesel, Frederik L. A1 - Kratochwil, Clemens A1 - Schlittenhardt, Joel A1 - Dendl, Katharina A1 - Eiber, Matthias A1 - Staudinger, Fabian A1 - Kessler, Lukas A1 - Fendler, Wolfgang P. A1 - Lindner, Thomas A1 - Koerber, Stefan A. A1 - Cardinale, Jens A1 - Sennung, David A1 - Roehrich, Manuel A1 - Debus, Juergen A1 - Sathekge, Mike A1 - Haberkorn, Uwe A1 - Calais, Jeremie A1 - Serfling, Sebastian A1 - Buck, Andreas L. T1 - Head-to-head intra-individual comparison of biodistribution and tumor uptake of \(^{68}\)Ga-FAPI and \(^{18}\)F-FDG PET/CT in cancer patients JF - European Journal of Nuclear Medicine and Molecular Imaging N2 - Purpose FAPI ligands (fibroblast activation protein inhibitor), a novel class of radiotracers for PET/CT imaging, demonstrated in previous studies rapid and high tumor uptake. The purpose of this study is the head-to-head intra-individual comparison of \(^{68}\)Ga-FAPI versus standard-of-care \(^{18}\)F-FDG in PET/CT in organ biodistribution and tumor uptake in patients with various cancers. Material and Methods This international retrospective multicenter analysis included PET/CT data from 71 patients from 6 centers who underwent both \(^{68}\)Ga-FAPI and \(^{18}\)F-FDG PET/CT within a median time interval of 10 days (range 1–89 days). Volumes of interest (VOIs) were manually drawn in normal organs and tumor lesions to quantify tracer uptake by SUVmax and SUVmean. Furthermore, tumor-to-background ratios (TBR) were generated (SUVmax tumor/ SUVmax organ). Results A total of 71 patients were studied of, which 28 were female and 43 male (median age 60). In 41 of 71 patients, the primary tumor was present. Forty-three of 71 patients exhibited 162 metastatic lesions. \(^{68}\)Ga-FAPI uptake in primary tumors and metastases was comparable to 18F-FDG in most cases. The SUVmax was significantly lower for \(^{68}\)Ga-FAPI than \(^{18}\)F-FDG in background tissues such as the brain, oral mucosa, myocardium, blood pool, liver, pancreas, and colon. Thus, \(^{68}\)Ga-FAPI TBRs were significantly higher than 18F-FDG TBRs in some sites, including liver and bone metastases. Conclusion Quantitative tumor uptake is comparable between \(^{68}\)Ga-FAPI and \(^{18}\)F-FDG, but lower background uptake in most normal organs results in equal or higher TBRs for \(^{68}\)Ga-FAPI. Thus, \(^{68}\)Ga-FAPI PET/CT may yield improved diagnostic information in various cancers and especially in tumor locations with high physiological \(^{18}\)F-FDG uptake. KW - FAPI PET/CT KW - FDG PET/CT KW - cancer-associated fibroblast KW - various cancer diseases Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-307252 SN - 1619-7070 SN - 1619-7089 VL - 48 IS - 13 ER -