Acetyl-lys-lys-lys-lys-lys-cys-gly-cys-gly-gly-pro-leu-tyr-lys-lys-ile-ile-lys-lys-leu-leu-glu-ser-heparin-[Tc]

Because of their ability to accumulate at sites of infection and inflammation, the leukocyte and monocyte components of the white blood cell (WBC) have often been labeled under conditions with radioisotopes such as indium (In), meta-stable technetium (Tc), or radioactive compounds such as Tc-gluceptate, [Ga]gallium citrate, and Tc-labeled antibodies, etc (1). Radiolabeling of leukocytes or monocytes involves the isolation of these cells from the WBC pool, a process that is slow and expensive, involves the handling of blood, and can lead to contamination of the samples. In addition, the labeled cells have a slow clearance from circulation and may be imaged up to 24 h after administration to allow time for accumulation at the site of infection or inflammation. Also, these imaging agents usually have a low signal-to-noise ratio, especially during the early time points, and show a high intestinal uptake that interferes with diagnostic imaging of the abdominal area (2). Radioactively labeled monoclonal antibodies have been used for the imaging of infections, but these radiopharmaceuticals have limited application because they also have a slow clearance from circulation and are not always sensitive enough to detect pulmonary or bone infections (3, 4). In addition, labeled antibodies have been shown to induce transient neutropenia and the formation of human anti-mouse antibodies (HAMA) (4, 5). The HAMA response can limit the repeat use of the antibodies because it neutralizes and alters the biodistribution of the agent (6). The use of peptides to detect sites of infection or inflammation is an attractive option because these compounds are cheap and easy to synthesize, can be modified to suit target requirements, and show rapid clearance from circulation (7, 8). Chemotactic peptides have been developed and evaluated for the imaging of infections and inflammation, but these compounds have limitations because the buffer components used to label the peptides may influence their biodistribution characteristics (8). Moyer et al. identified and developed a heparin-binding peptide, P483, for the imaging of infections (9). The sequence of this peptide was based on the platelet factor-4 heparin-binding region. The peptide comprises 23 amino acids, was modified to contain a lysine-rich region to allow rapid renal clearance, and could be labeled with Tc. The peptide was complexed with heparin and labeled with Tc to generate Tc-P483H, a peptide that targets leukocytes (9). Conjugation of the peptide with heparin enhanced the binding of the labeled peptide to WBC. The labeled peptide was evaluated for the imaging of infections in a rabbit model and also in humans (9, 10).