Publikationsrepositorium - Helmholtz-Zentrum Dresden-Rossendorf

The utilization of dendrimers in medicine holds great potential in emerging applications of diagnostic imaging, as well as the promise of new capabilities for delivering therapies tailored and targeted for specific diseases. In this perspective, radiolabeled dendritic frameworks are gaining in importance, particularly for the use in tumor imaging and therapy.[1] Pegylation as well as carbohydration of radiolabeled compounds is of considerable interest to improve the pharmacokinetics, biocompatibility, and tumor accumulation.[2,3]
In this context, DOTA-modified glycodendrimers with dense maltose shell (Figure: structure of 4th generation dendrimer) were selected from the point of view to use the highly homogenous dendritic structure for improved tumor imaging and therapy and to enhance the biocompatibility of dendrimers by the decoration with carbohydrates. The outcome of the synthetic effort was the synthesis of 4th and 5th generation glycodendrimers with the variation of chemically attached DOTA chelators (1, 3, 9 DOTA units/4th generation dendrimer; 9 and 18 DOTA units/5th generation dendrimer), which form stable complexes with a large number of radiometals. The multivalent decoration with DOTA on dendrimer surface was also stimulated by the facts that radiolabeling kinetics can be accelerated and to achieve enhanced specific activity.
The labeling conditions of the glycodendrimers synthesized with 64Cu were optimized, and the influence of reaction time, temperature, buffer conditions and the dendrimer amount on the radiochemical yield were studied using Radio-TLC and Radio-SEC. The radiocopper(II) complexes of the DOTA-functionalized glycodendrimers show a high in vitro stability. Preliminary biodistribution studies of ⁶⁴Cu-labeled 4th generation dendrimers with maltose shell in healthy Wistar rats indicate the preferred accumulation in the liver.