RESUMEN
Molecular imaging offers the possibility to investigate biological and biochemical processes non-invasively and to obtain information on both anatomy and dysfunctions. Based on the data obtained, a fundamental understanding of various disease processes can be derived and treatment strategies can be planned. In this context, methods that combine several modalities in one probe are increasingly being used. Due to the comparably high sensitivity and provided complementary information, the combination of nuclear and optical probes has taken on a special significance. In this review article, dual-labelled systems for bimodal nuclear and optical imaging based on both modular ligands and nanomaterials are discussed. Particular attention is paid to radiometal-labelled molecules for single-photon emission computed tomography (SPECT) and positron emission tomography (PET) and metal complexes combined with fluorescent dyes for optical imaging. The clinical potential of such probes, especially for fluorescence-guided surgery, is assessed.
RESUMEN
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.
RESUMEN
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.
