Peptide-based positron emission tomography probes: current strategies for synthesis and radiolabelling

In medical imaging, techniques such as magnetic resonance imaging, contrast-enhanced computerized tomography, and positron emission tomography (PET) are extensively available and routinely used for disease diagnosis and treatment. Peptide-based targeting PET probes are usually small peptides with high affinity and specificity to specific cellular and tissue targets opportunely engineered for acting as PET probes. For instance, either the radioisotope (e.g., ¹⁸F, ¹¹C) can be covalently linked to the peptide-probe or another ligand that strongly complexes the radioisotope (e.g., ⁶⁴Cu, ⁶⁸Ga) through multiple coordinative bonds can be chemically conjugated to the peptide delivery moiety. The main advantages of these probes are that they are cheaper than classical antibody-based PET tracers and can be efficiently chemically modified to be radiolabelled with virtually any radionuclide making them very attractive for clinical use. The goal of this review is to report and summarize recent technologies in peptide PET-based molecular probes synthesis and radiolabelling with the most used radioisotopes in 2022.