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

Abstract

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 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 (Ki's in the 0.25 - 10 nM range) compared favorably with [DTPA]octreotide (Ki = 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 Ki'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 99m Tc-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.

A Molecular Imaging Primer: Modalities, Imaging Agents, and Applications

“…Peptide imaging agents can be used to visualize a range of targets, including integrins (20,57,294), matrix metalloproteinases (36,187), caspases (91,95), somatostatin receptors (82,136,331), neuropeptide Y receptor (253,485), and gastrin releasing peptide receptor (372,427,428). See TABLE 2 for some specific examples of peptide molecular imaging agents that can be used for optical, PET, and SPECT imaging.…”

Radiolabeling of MAG3-morpholino oligomers with 188Re at high labeling efficiency and specific radioactivity for tumor pretargeting

“…In the case of carriers that can withstand harsh environments, post-conjugation labeling should be possible and more practical. However, although a few post-conjugation 188 Re labeling have been reported (Guhlke et al, 1998;Pearson et al, 1996;Zinn et al, 2000;Polyakov et al, 2000;Gestin et al, 2001), to our knowledge, none describes 188 Re labeling of a biomolecule at high labeling efficiency and high specific radioactivity. This laboratory has been using S-acetyl protected and N-hydroxysuccinimide-activated MAG 3 ester for 99m Tc labeling.…”

Isolation, Characterization, and Biological Evaluation ofSynandAntiDiastereomers of [99mTc]Technetium Depreotide: a Somatostatin Receptor Binding Tumor Imaging Agent

“…8 The 99m Tc-labeled agent, [ 99m TcO]depreotide, has received regulatory approval in the United States and Europe for use in the detection of malignant lung cancer. [ 99m TcO]depreotide binds to a wider range of somatostain receptor subtypes (SSTR2, SSTR3, and SSTR5) 9 than octreotide and its radiolabeled derivatives (mainly these bind to SSTR2 10,11 ) and, therefore, may be useful for diagnosing a broader range of tumor types.…”