Department of Chemistry | University of Zurich

Department of Chemistry | University of Zurich

@chem.uzh.ch

102 followers69 following66 posts

Department of Chemistry | University of Zurich
@chem.uzh.ch

Congratulation to Momir Malis from the Luber Group on winning a SNSF Spark Grant (Spark Grants are for rapid funding of novel and unconventional ideas) for his project: Improving the variational density functional theory for excited electronic states with machine learning 👏

Department of Chemistry | University of Zurich reposted

Patrick Cieslik
@pacieslik.bsky.social

Happy to share that my second paper from the @hollandlab.bsky.social is online now! We have discovered a new bioconjugation strategy and have tested it in terms of Radioimmunotherapy with Tb-161! Thanks to all authors! doi.org/10.1021/jacs...

doi.orgLight-Induced Synthesis and Radiotheranostic Treatment of Gastric Cancer with 161Tb-Labeled Monoclonal AntibodiesRadiolabeled monoclonal antibodies (mAbs) form a major branch of nuclear medicine and are used in the development of tracers for both diagnostic imaging and molecularly targeted radio(immuno)therapy (RIT). Since treatment options for many types of late-stage cancers are limited and these diseases become refractory to classic chemotherapy, new tools are required to improve patient outcomes. The high tumor uptake and specificity of mAbs, coupled with increased therapeutic range of energetic β–-emitting radionuclides, offers a potential solution to overcome traditional problems associated with poor tissue penetration of antibody-drug conjugates, chemotherapeutic resistance, and off-target accumulation, which can lead to adverse responses. The challenge is to develop efficient and reliable chemical methods that provide simultaneous selectivity and high stabilization of the radiometal via complexation chemistry, with rapid access to new bioconjugate bonds on protein that avoid the loss of bioactivity. Here, we designed a new octadentate bispidine-chelating system, functionalized with a light-responsive tetrazole unit, and demonstrated the chemoselective derivatization of sulfhydryl groups introduced on the protein surface. High radiolabeling and bioconjugation yields of 161Tb-onartuzumab─an engineered mAb fragment targeting the human hepatocyte growth-factor receptor (c-MET; a characteristic biomarker found in clinical samples of several diseases, including gastric adenocarcinomas)─were obtained under ambient conditions after 5 min of light-induced coupling. Comprehensive biochemical and animal experiments including cellular binding assays, noninvasive γ-ray imaging, biodistribution studies, and pharmacokinetic measurements established the viability of using 161Tb-onartuzumab to target c-MET expression in vivo. Subsequent RIT studies in MKN-45 xenograft models demonstrated that the 161Tb-onartuzumab radiotracer formed by photoradiosynthesis permitted low-dose therapy studies that led to efficient targeting and treatment of tumor models. Collectively, the new complexation and chemoselective photoconjugation chemistries overcome some of the limitations in traditional labeling approaches. Photoradiosynthesis represents an excellent platform for building future antibody-based radiotracers for applications in diagnostic and therapeutic medicine.