Radiolabeling with the promising radionuclide 45Ti and their immobilization on relevant peptides and development of peptide-chelator conjugates for immuno-PET imaging applications will be in focus.
We are aiming to implement an efficient method for 45Ti isotope trapping via diol- functionalized resins, subsequently study the decomplexation of resin-bound 45Ti by wrapping the titanium with multidentate and hydrophilic chelators that can either directly or in a separate step be conjugated to pre-functionalized peptides. The development a method that allows for this to take place in aqueous solution will be a major focus of WP2. A large part of the work will be dedicated to shortening and simplify the preparation procedures and at the same time increasing the hydrolytic stability of titanium compounds. In order to further extend the synthetic methodology based on 45Ti complexes as radiotracers, peptides bearing specific epitopes for binding to tumor-cell specific proteins will be targeted as radiometal carriers for expanding its applicability toward imaging applications. For this purpose, post-functionalization of water-soluble peptides allowing the transfer in aqueous phase of the capped 45Ti complexes with multidentate hydrophilic chelators will be investigated, with a particular focus on their kinetic inertness under in vivo conditions. To support the pre-clinical activities, lead by Tromsø, peptide candidates with appropriate metal chelator functionality for 64Cu, 89Zr, 177Lu and 225Ac will be prepared by our experts.
Work package 1:
In WP1 “Precursor and Radiolabeling Methodology” we will use contemporary organic synthesis strategies for preparing facile radiolabeling substituents. This will include catalytic functionalization for 18F or 11C labeling, solid supported resin-bound methods and other late stage functionalization strategies. The strategies explored here will also be developed into methods for instrumental radiolabeling using current radiosynthesis modules…
Work package 2:
Radiolabeling with the promising radionuclide 45Ti and their immobilization on relevant peptides and development of peptide-chelator conjugates for immuno-PET imaging applications will be in focus. We are aiming to implement an efficient method for 45Ti isotope trapping via diol- functionalized resins, subsequently study the decomplexation of resin-bound 45Ti by wrapping the titanium with multidentate and…
Work package 3:
This work package will draw the current consortium wide expertise in kinase inhibitors (KIs) and jointly develop small molecule KIs for imaging and treatment of brain tumors. To achieve our goals we will utilize a dual strategy: Development of novel KIs radiolabeled with 11C and 18F and development of novel bioconjugates containing a therapeutic radiometal….
Work package 4:
Development of new tracers takes on average 13 years, similar to other pharmaceuticals. In order to increase patient care and precision diagnostics during the timeframe of this project, much attention will be given to WP4 “Tracer Implementation” to increase the number of locally available PET tracers. Due to the aforementioned costs associated with transport and…