Somatostatin Receptor-Binding Peptides Labeled with Technetium-99m:  Chemistry and Initial Biological Studies

• Published in: Journal of medicinal chemistry Vol. 39; no. 7; pp. 1361 - 1371
• Main Authors: Pearson, Daniel A, Lister-James, John, McBride, William J, Wilson, David M, Martel, Lawrence J, Civitello, Edgar R, Taylor, John E, Moyer, Brian R, Dean, Richard T
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 29.03.1996
• Subjects: Amino Acid Sequence; Animals; Biological and medical sciences; Chelating Agents - chemical synthesis; Chelating Agents - metabolism; Digestion. Liver. Biliary tract. Spleen. Pancreas; Humans; Investigative techniques, diagnostic techniques (general aspects); Mass Spectrometry; Medical sciences; Molecular Sequence Data; Molecular Structure; Octreotide - analogs & derivatives; Octreotide - metabolism; Oligopeptides - chemical synthesis; Oligopeptides - metabolism; Oligopeptides - pharmacokinetics; Pancreatic Neoplasms - metabolism; Pentetic Acid - analogs & derivatives; Pentetic Acid - metabolism; Peptides, Cyclic - chemical synthesis; Peptides, Cyclic - metabolism; Peptides, Cyclic - pharmacokinetics; Protein Binding; Radionuclide investigations; Rats; Receptors, Somatostatin - metabolism; Rhenium - metabolism; Somatostatin - analogs & derivatives; Somatostatin - metabolism; Somatostatin - pharmacokinetics; Technetium Compounds - chemical synthesis; Technetium Compounds - metabolism; Technetium Compounds - pharmacokinetics; Tumor Cells, Cultured; Radionuclide study; Intravenous administration; Oligopeptides; Rat; Ligand; Cyclic peptides; Technetium V Complexes; Tissue; Target; Indium Complexes; Structure activity relation; Rhenium Complexes; Diagnosis; Somatostatin; Chemical synthesis; Pancreatic disease; Human; Indium 111; Radiolabelling; Rodentia; Organic ligand; Transition metal Complexes; Malignant tumor; In vitro; Oxo complex; In vivo; Vertebrata; Biological fixation; Experimental disease; Mammalia; Sulfur peptide; Animal; Distribution; Peptide synthesis; Solid phase; Pharmacokinetics; Hormonal receptor
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm950111m

The synthesis of peptides which possess a high affinity for the somatostatin receptor and contain a chelator for the radionuclide technetium-99m is described. The target compounds were designed such that they would form stable, oxotechnetium(V) chelate complexes in which the site of metal coordination was well defined and remote from the receptor-binding region. Oxorhenium(V) chelate complexes of these peptides were prepared as nonradioactive surrogates for the technetium complexes. Peptide oxorhenium complexes and Tc-99m complexes eluted closely upon HPLC analysis. The receptor-binding affinities of both the free and rhenium-coordinated species were measured in vitro. The binding affinities of the free peptides (K i's in the 0.25−10 nM range) compared favorably with [DTPA]octreotide (K i = 1.6 nM), which, as the indium-111 complex, is already approved for somatostatin receptor (SSTR)-expressing tumor imaging in the United States and Europe. Furthermore, the rhenium-coordinated peptides had binding affinities which, in many cases, were higher than those of the corresponding free peptides, with several complexes having a K i's of 0.1 nM. Some of the more potent SSTR-binding peptides were labeled with technetium-99m and assessed in an in vivo study with tumor-bearing rats. The 99mTc-labeled peptides prepared in this study should be useful as SSTR-expressing tumor-imaging agents due to their high SSTR-binding affinities, ease of preparation, and, because they are low molecular weight peptides, expected pharmacokinetics characterized by rapid tracer excretion from the body resulting in high-contrast images.