Radiopharmaceutical evaluation of novel bifunctional chelators and bioconjugates for tumor imaging and therapy

The development of multi-functional complexing agents for radiometal nuclides with a view of nuclear medical application represents a field of research that is intensively dealt with and has rapidly been developing. In this context, ligands that form highly stable metal complexes and additionally possess several different functional groups are of particular interest. This enables the simultaneous introduction of targeting, solubilizing and, for example, fluorescent units into the relevant metal complexes. In this perspective, bifunctional chelating agents (BFCAs) based on 3,7-diazabicyclo[3.3.1]nonane (bispidine) and 1,4,7-triazacyclononane (TACN) are discussed. Examples of target-specific peptides and bio(nano)materials equipped with bispidine and TACN ligands for labeling with 64Cu as an ideal positron emitter are presented. This enables tumor imaging and the biodistribution of the materials to be studied over a period of days via positron emission tomography (PET). This lecture will also give an insight into the pre-targeting strategy using complementary oligonucleotides such as peptide nucleic acid (PNA) derivatives. The pre-targeting strategy allows for the rational use of long circulating, high affinity antibodies for both non-invasive cancer radioimmunodetection (RID) and –therapy (RIT).