Search

Bifunctional chelators as parts of modular metal‐based radiopharmaceuticals are responsible for stable complexation of the radiometal ion and for covalent linkage between the complex and the targeting vector. To avoid loss of complex stability, the bioconjugation strategy should not interfere with the radiometal chelation by occupying coordinating groups. The C9 position of the very stable CuII chelator 3,7‐diazabicyclo[3.3.1]nonane (bispidine) is virtually predestined to introduce functional groups for facile bioconjugation as this functionalisation does not disturb the metal binding centre. We describe the preparation and characterisation of a set of novel bispidine derivatives equipped with suitable functional groups for diverse bioconjugation reactions, including common amine coupling strategies (bispidine‐isothiocyanate) and the Cu‐free strain‐promoted alkyne–azide cycloaddition. We demonstrate their functionality and versatility in an exemplary way by conjugation to an antibody‐based biomolecule and validate the obtained conjugate in vitro and in vivo., Ready for bioconjugation: Modification of the bispidine backbone at the C9‐position via an ether linkage provides a set of suitable bifunctional chelators ready for incorporating into targeting moieties and 64CuII‐labelling. The usefulness of these bifunctional chelators for targeted positron emission tomography (PET) imaging is demonstrated in vivo.

Iron and copper are essential micronutrients needed for the proper function of every cell. However, in excessive amounts, these elements are toxic, as they may cause oxidative stress, resulting in damage to the liver and other organs. This may happen due to poisoning, as a side effect of thalassemia infusion therapy or due to hereditary diseases hemochromatosis or Wilson’s disease. The current golden standard of therapy of iron and copper overload is the use of low-molecular-weight chelators of these elements. However, these agents suffer from severe side effects, are often expensive and possess unfavorable pharmacokinetics, thus limiting the usability of such therapy. The emerging concepts are polymer-supported iron- and copper-chelating therapeutics, either for parenteral or oral use, which shows vivid potential to keep the therapeutic efficacy of low-molecular-weight agents, while avoiding their drawbacks, especially their side effects. Critical evaluation of this new perspective polymer approach is the purpose of this review article.