Tetraamine-Coupled Peptides and Resulting 99mTc-Radioligands: An Effective Route for Receptor-Targeted Diagnostic Imaging of Human Tumors

The successful application of OctreoScan® ([111In-DTPA]octreotide) in the diagnosis of sst2-expressing neuroendocrine tumors (NETs), on one hand, and the manifestation of peptide receptor targets in a wide range of human cancers, on the other, have synergistically induced a booming emergence of numerous radiolabeled peptide (radiopeptide) probes for tumor diagnosis and therapy in man. Definition of molecular targets and their relation to neoplastic disease has preceded peptide-based radiopharmaceutical design and development. New criteria have been set to safeguard efficient localization of radionuclides on tumor-associated high affinity – low capacity peptide receptor systems. New technical and biological terms, such as specific activity or receptor affinity and internalization, have invaded the Radiopharmacy domain and have irrevocably altered our concept of radiopharmaceutical design. Nonetheless, 99mTc remains the gold standard of diagnostic nuclear medicine as a result of ideal nuclear characteristics, cost-effectiveness and wide availability in high purity and high specific activity by means of commercial 99Mo/99mTc-generators. The evolution of conventional 99mTc-perfusion agents into modern state-of-the-art molecular radiopharmaceuticals has been a challenge addressed by several researchers. The present review summarizes recent advances in the development of 99mTc-labeled peptides for in vivo targeting of neoplastic disease, and, in particular, those functionalized with acyclic tetraamines. Conclusions on their applicability in non-invasive diagnosis and staging of cancer patients are drawn.