Synthesis, Characterization and Evaluation of Radiometal-Containing Peptide Nucleic Acids

As described in Chapter, peptide nucleic acids (PNAs) have very attractive properties, which include, among them, high selectivity towards DNA/RNA recognition. It is therefore not surprising that their potential in nuclear medicine and biology to explore in vitro and in vivo processes has also been investigated. The high thermal and radiolytic stability as well as resistance toward nuclease/protease degradation of these bioconjugates offers new opportunities in this field of research, which could, potentially, lead to a transformation of the whole scope of diagnostically and therapeutically relevant radionuclides. Importantly, as demonstrated in Chapter with metal complexes, PNAs can be synthetically modified allowing their intrinsic physico-chemical properties to be significantly modulated. For example, the attachment of appropriate spacer elements and specific building blocks, such as targeting units, to both the C- and N-terminus of PNAs allows a broad variation of the pharmacologic properties of PNA bioconjugates, hence enabling the development of application-orientated probes for imaging of gene expression. Furthermore, the high metabolic resistance of these non-natural oligonucleotides makes them interesting for therapeutic applications. In this book chapter, we report on the current developments towards the preparation of radiometal-containing PNA constructs and summarize the protocols for labeling these oligonucleotides with ^99mTc, ¹¹¹In, ⁶⁴Cu, ⁹⁰Y and ¹⁷⁷Lu.