Iod-Tetrazine für die Bioorthogonale Radiotheranostik

Abstract

The application of various radionuclides of iodine is particularly indispensable in the field of nuclear medicine. The intravenous administration of radiopharmaceuticals containing 123I, 124I, 125I or 131I, is an effective treatment for a number of tumors and diseases such as non-Hodgkin-lymphoma, prostate, breast, skin or thyroid cancer. The versatility of these nuclides enables ¿theranostic¿ approaches in modern oncology. Hence, the combination of diagnostic imaging tools, such as positron emission tomography (PET) or single photon emission computer tomography (SPECT), for visualization of the malignant tissue with therapeutic applications can be realized without changing the agent's pharmacokinetics. To allow the use of compounds with short half-life or slow accumulation, bioorthogonal strategies can be applied. Following a two-step process, a non-radioactive marker reagent is administered that accumulates in the target tissue. In the second step, a radioactive agent is given, which selectively binds in vivo to the marker within a bioorthogonal reaction. Improved pharamcokinetics of both compounds are key to the success of the overall pretargeting approach. In this context, based on the bioorthogonal IEDDA ("Inverse Electron Demand Diels-Alder") reaction between tetrazines and strained alkenes, numerous unsymmetrically substituted iodo-1,2,4,5-tetrazines were synthesized in the course of this thesis following two different strategies. Figure 1 Selected 1,2,4,5-tetrazines were successfully radiolabeled with iodine-125. These probes showed high IEDDA reaction rates and promising stabilities in human blood plasma