Homing agents
The present disclosure provides peptide constructs for diagnostic imaging and therapeutic applications, using pegylated peptides which exhibit specific binding for a target molecule of interest, such as a biomarker of a disease or disorder.
1. A p-armed multimer, each arm of the multimer comprising:
a polymer comprising n PEG monomers, wherein n is at least 2;
a linker comprising His-His-Glu; and
a homing molecule selected from the group consisting of an antibody, an aptamer, and a peptide, wherein the homing molecule binds a biomarker of thrombosis,
wherein the homing molecule is linked to the C-terminus of the linker, and the polymer is linked via an amino acid side chain of the linker; and
wherein p is at least 3, and each arm of the multimer is bound to the other arms of the multimer via an end of the polymer not attached to the linker;
wherein the p-armed multimer further comprises at least one diagnostic and/or therapeutic agent attached to an N-terminus of the linker of that arm, wherein the at least one diagnostic agent or therapeutic agent is a radioisotope of technetium or a radioisotope of rhenium.
2. A p-armed multimer of claim 1 , wherein the biomarker of thrombosis is selected from the group consisting of fibrin and ICAM.
3. A p-armed multimer of claim 1 , wherein the radionuclide is selected from the group consisting of 99m Tc, 186 Re, and 188 Re.
4. A p-armed multimer of claim 1 , comprising a diagnostic agent on at least one arm and a therapeutic agent on at least one other arm.
5. A radiopharmaceutical composition comprising a p-armed multimer of claim 1 , together with a pharmaceutically-acceptable carrier.
6. A method for detecting intradevice thrombus in a subject having an implanted mechanical circulation assist device, the method comprising:
(a) administering into the bloodstream of the subject an effective amount of the p-armed multimer of claim 1 ;
(b) allowing the p-armed multimer to bind thrombus; and
(c) detecting a signal from the radioisotope of the p-armed multimer localized at a site of thrombus.
7. The method of claim 6 , wherein the method further comprises quantifying intradevice thrombus by: (d) determining the amount of p-armed multimer localized at a site of thrombus from the signal detected, wherein the amount of p-armed multimer is indicative of the size of the thrombus.
8. A p-armed multimer of claim 1 , wherein the homing molecule is attached to the C-terminus of the linker via a hydrophilic moiety.
9. A p-armed multimer of claim 1 , wherein n is 2 to 60.
10. A p-armed multimer, each arm of the multimer comprising:
a polymer comprising n PEG monomers, wherein n is at least 2;
a linker comprising His-His-Glu; and
a homing molecule that is an antibody, wherein the homing molecule binds a target molecule;
wherein the homing molecule is linked to the C-terminus of the linker, and the polymer is linked via an amino acid side chain of the linker; and
wherein p is at least 3, and each arm of the multimer is bound to the other arms of the multimer via an end of the polymer not attached to the linker;
wherein the p-armed multimer further comprises at least one diagnostic and/or therapeutic agent attached to an N-terminus of the linker of that arm, wherein the at least one diagnostic agent or therapeutic agent is a radioisotope of technetium or a radioisotope of rhenium.
11. A p-armed multimer of claim 10 , wherein the target molecule is a biomarker of thrombosis.
12. A p-armed multimer of claim 10 , wherein the target molecule is selected from the group consisting of fibrin and ICAM.
13. A p-armed multimer of claim 10 , wherein n is 2 to 60.
14. A p-armed multimer of claim 10 , wherein the N-terminus of the homing molecule is attached to the C-terminus of the linker using a hydrophilic moiety.
15. A p-armed multimer, each arm of the multimer comprising:
a polymer comprising n PEG monomers, wherein n is at least 2;
a linker comprising His-His-Glu; and
a homing molecule comprising SEQ ID NO: 1;
wherein the homing molecule is linked to the C-terminus of the linker, and the polymer is linked via an amino acid side chain of the linker; and
wherein p is at least 3, and each arm of the multimer is bound to the other arms of the multimer via an end of the polymer not attached to the linker;
wherein the p-armed multimer further comprises at least one diagnostic and/or therapeutic agent attached to an N-terminus of the linker of that arm, wherein the at least one diagnostic agent or therapeutic agent is a radioisotope of technetium or a radioisotope of rhenium.
16. A p-armed multimer of claim 15 , wherein the homing molecule is attached to the C-terminus of the linker via a hydrophilic moiety.
17. A p-armed multimer of claim 15 , wherein n is 2 to 60.