A ticket to ride: peptide radiopharmaceuticals.

Over the past three decades, biospecific imaging agents have evolved from large proteins (i.e., antibodies) to antibody fragments (i.e., F(ab')2 and Fab fragments) to smaller "molecular recognition units" such as Fv fragments, antigen binding domain fragments and small biologically active peptides. The smaller size of these molecules confers desirable pharmacokinetic properties, such as higher target-to-background ratios and faster blood clearance, that are favorable for imaging. Molecular engineering techniques now permit the peptide to carry the radionuclide-binding group in its structure while maintaining high-affinity binding to the receptor site. An important component to this system is the ability to radiolabel these agents with high specific activity using short-lived radionuclides, particularly 99mTc. Recently, the application of small radiolabeled biologically active peptides for external imaging of a variety of biological processes has received considerable interest. These applications have ranged from the current widespread use of somatostatin analogs for imaging numerous types of tumors to the development of radiolabeled chemotactic peptides for infection imaging. In this review, we will describe many of the parameters for the rational development of peptide-based imaging agents, including: classes of peptides for imaging, methods for radiolabeling peptides, current biologically active peptide-based radiopharmaceuticals and future prospects for this new technology.