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|Title:||Technetium-99M labeled peptides for thrombus imaging|
|Abstract:||This invention relates to radiolabeled peptides and methods for producing such peptides. Specifically, the invention relates to specific binding peptides, methods and kits for making such peptides, and methods for using such peptides labeled with technetium-99m via a radiolabel-binding moiety covalently linked to the peptide to image thrombus sites in a mammalian body.|
|Inventor(s):||Dean; Richard T. (Bedford, NH), Lister-James; John (Bedford, NH)|
|Assignee:||Diatide, Inc. (Londonderry, NH)|
|Filing Date:||Jul 11, 1994|
|Claims:||1. A reagent for preparing a thrombus imaging agent for imaging a thrombus within a mammalian body comprising a specific binding peptide and a technetium-99m binding moiety covalently linked to the specific binding peptide, wherein the peptide binds to a component of a thrombus, the technetium-99m binding moiety having formula: |
wherein C(pgp).sup.s is a cysteine having a protected thiol group and (aa) is an amino acid.
2. The reagent of claim 1 wherein the specific binding peptide and C(pgp).sup.s -(aa)-C(pgp).sup.s are covalently linked through from about one to about twenty amino acids.
3. The reagent of claim 1 wherein the protected cysteine has a protecting group of the formula
wherein R is a lower alkyl having 1 to 6 carbon atoms, 2-,3-,4-pyridyl, phenyl, or phenyl substituted with lower alkyl, hydroxy, lower alkoxy, carboxy, or lower alkoxycarbonyl.
4. The reagent of claim 1 wherein C(pgp).sup.s -(aa)-C(pgp).sup.s has the formula: ##STR17##
5. The reagent of claim 1 having the formula: ##STR18##
6. The reagent of claim 1 having the formula ##STR19##
7. A kit for preparing a radiopharmaceutical preparation, said kit comprising a sealed vial containing a predetermined quantity of the reagent of claim 1 and a sufficient amount of reducing agent to label the reagent with technetium-99m.
8. The reagent according to claim 1 wherein the specific-binding peptide is chemically synthesized in vitro.
9. The reagent according to claim 8 wherein the specific-binding peptide is synthesized by solid phase peptide synthesis.
10. The reagent according to claim 8 wherein the radiolabel-binding moiety is covalently linked to the specific-binding peptide during in vitro chemical synthesis.
11. The reagent according to claim 10 wherein the radiolabel-binding moiety is covalently linked to the specific-binding peptide during solid phase peptide synthesis.
12. A composition of matter comprising the reagent according to claim 1 wherein the specific binding peptide is selected from the group consisting of peptides having the amino acid sequence: ##STR20##
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