Somatostatin receptor-binding peptides labeled with technetium-99m: Chemistry and initial biological studies

Daniel A. Pearson, John Lister-James, William J. McBride, David M. Wilson, Lawrence J. Martel, Edgar R Civitello, John E. Taylor, Brian R. Moyer, Richard T. Dean

Research output: Contribution to journalArticle

90 Citations (Scopus)

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 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.

Original languageEnglish (US)
Pages (from-to)1361-1371
Number of pages11
JournalJournal of Medicinal Chemistry
Volume39
Issue number7
DOIs
StatePublished - Mar 29 1996
Externally publishedYes

Fingerprint

Somatostatin Receptors
Technetium
Peptides
Rhenium
Tumors
Bearings (structural)
Imaging techniques
Neoplasms
Pentetic Acid
Indium
Pharmacokinetics
Octreotide
Chelating Agents
Radioisotopes
Rats
Molecular Weight
Metals
Molecular weight
High Pressure Liquid Chromatography

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Pearson, D. A., Lister-James, J., McBride, W. J., Wilson, D. M., Martel, L. J., Civitello, E. R., ... Dean, R. T. (1996). Somatostatin receptor-binding peptides labeled with technetium-99m: Chemistry and initial biological studies. Journal of Medicinal Chemistry, 39(7), 1361-1371. https://doi.org/10.1021/jm950111m

Somatostatin receptor-binding peptides labeled with technetium-99m : Chemistry and initial biological studies. / 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.

In: Journal of Medicinal Chemistry, Vol. 39, No. 7, 29.03.1996, p. 1361-1371.

Research output: Contribution to journalArticle

Pearson, DA, Lister-James, J, McBride, WJ, Wilson, DM, Martel, LJ, Civitello, ER, Taylor, JE, Moyer, BR & Dean, RT 1996, 'Somatostatin receptor-binding peptides labeled with technetium-99m: Chemistry and initial biological studies', Journal of Medicinal Chemistry, vol. 39, no. 7, pp. 1361-1371. https://doi.org/10.1021/jm950111m
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. / Somatostatin receptor-binding peptides labeled with technetium-99m : Chemistry and initial biological studies. In: Journal of Medicinal Chemistry. 1996 ; Vol. 39, No. 7. pp. 1361-1371.
@article{ca80a9dbbcd34151a497e72d0f505f85,
title = "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 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.",
author = "Pearson, {Daniel A.} and John Lister-James and McBride, {William J.} and Wilson, {David M.} and Martel, {Lawrence J.} and Civitello, {Edgar R} and Taylor, {John E.} and Moyer, {Brian R.} and Dean, {Richard T.}",
year = "1996",
month = "3",
day = "29",
doi = "10.1021/jm950111m",
language = "English (US)",
volume = "39",
pages = "1361--1371",
journal = "Journal of Medicinal Chemistry",
issn = "0022-2623",
publisher = "American Chemical Society",
number = "7",

}

TY - JOUR

T1 - Somatostatin receptor-binding peptides labeled with technetium-99m

T2 - Chemistry and initial biological studies

AU - Pearson, Daniel A.

AU - Lister-James, John

AU - McBride, William J.

AU - Wilson, David M.

AU - Martel, Lawrence J.

AU - Civitello, Edgar R

AU - Taylor, John E.

AU - Moyer, Brian R.

AU - Dean, Richard T.

PY - 1996/3/29

Y1 - 1996/3/29

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0029989477&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029989477&partnerID=8YFLogxK

U2 - 10.1021/jm950111m

DO - 10.1021/jm950111m

M3 - Article

C2 - 8691466

AN - SCOPUS:0029989477

VL - 39

SP - 1361

EP - 1371

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

SN - 0022-2623

IS - 7

ER -