Work

Isopeptidic Desferrioxamine Analogues: The Role of Hydroxamate Spacing for Chelation of Zr4+

Year: 2024

Type: article

Abstract: [89Zr]Zr4+ is a radionuclide of increasing clinical relevance for PET (positron emission tomography). However, an ideal chelator for stable Zr‐chelation remains to be discovered. This study describes the solid‐phase synthesis of octadentate Zr‐chelators based on an isopeptidic (ip) scaffold derived from the natural siderophore desferrioxamine (DFOB). Several analogues with different spacers separating the chelating hydroxamates have been prepared and converted to [89Zr]Zr‐complexes. The stability of these complexes was evaluated in human serum and in competition to excess of competing chelators. The assays revealed a beneficial effect of long hydroxamate spacing (9 atoms). Shorter spacing led to a decrease in complex stability. The most stable [89Zr]Zr‐ipDFO complex had a high stability in challenging competition experiments with a large excess of EDTA for 72 h as determined by radio TLC and LC/MS. The straightforward synthesis, high complex stability and a modular character make ipDFO derivatives promising chelators for applications in targeted PET.

Source: ChemMedChem

DOI: 10.1002/cmdc.202400890

Authors: Lasse Outzen, Darius Ludolfs, Maximilian Irl, Susanne Kossatz, Wolfgang Maison

Institutions: Universität Hamburg, TUM Klinikum, Technical University of Munich

Language: English

Topic: Radiopharmaceutical Chemistry and Applications

Subfield: Radiology, Nuclear Medicine and Imaging

Field: Medicine

Domain: Health Sciences

Open Access status: hybrid

Estimated APC paid: $3,950

Funder: Universität Hamburg