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US 8,133,472 B2Granted
Cyclopeptides containing RGD mimetics as imaging markers for integrins
AssigneeSiemens Medical Solutions USA, Inc.
InventorsHartmuth C. Kolb, Kai Chen, Joseph C. Walsh, Qianwa Liang
Life of this patent
Estimating the term…
Abstract
Radiolabeled cyclic polypeptides, pharmaceutical compositions comprising radiolabeled cyclic polypeptides, and methods of using the radiolabeled cyclic polypeptides. Such polypeptides can be used in imaging studies, such as Positron Emitting Tomography (PET) or Single Photon Emission Computed Tomography (SPECT).
Claims29
A cyclopeptide of formula I:
- wherein:
- R1 is selected from the group consisting of a side chain of a natural amino acid and a side chain of an unnatural amino acid, wherein the natural amino acid and the unnatural amino acid is either in the D or L form;
- R2 and R3 are each independently selected from the group consisting of —H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkyloxy, C1-C6 alkoxyalkyl, aryl, aryl-(C1-C6 alkylene)-, 3- to 7-membered carbocycle, 3- to 7-membered heterocycle, hydroxy-C1-C6-alkyl, and C1-C6-alkoxy-C1-C6-alkyl, wherein the alkyl, alkenyl, alkynyl, alkyloxy, alkoxyalkyl, aryl, carbocycle and heterocycle groups are each optionally substituted;
- R7 is absent or is selected from the group consisting of H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, aryl, aryl-(C1-C6 alkylene)-, a 3- to 7-membered carbocycle, and a 3- to 7-membered heterocycle, wherein the alkyl, alkenyl, alkynyl, aryl-alkylene, carbocycle and heterocycle groups are each optionally substituted;
- wherein R2, R3 and R7 are not all H;
- R8 is selected from the group consisting of a side chain of a natural amino acid and a side chain of an unnatural amino acid, wherein the natural amino acid and the unnatural amino acid is either in the D or L form;
- X is a 5 or 6-membered heterocycle or a linker comprising a hydrophilic moiety selected from the group consisting of hydroxyl, carbonyl, amide (—C(O)NH—), sulfonamide, sulfonate, phosphate, polar amino acid moiety, PEG moiety, sugar mimetic, and sugar moiety, or a combination thereof;
- Y is a 5 or 6-membered heterocycle, or a linker comprising a hydrophilic moiety selected from the group consisting of hydroxyl, carbonyl, sulfonamide, sulfonate, phosphate, polar amino acid moiety, PEG moiety, sugar mimetic, and sugar moiety;
- where at least one of X and Y is a 5 or 6-membered heterocycle;
- and
- w is 1, 2, 3, 4, or 5;
- wherein any one of X, Y, R2, R3, and R7 comprises a radionuclide selected from the group consisting of positron or gamma emitters.
9 more elements
A cyclopeptide of formula II:
- wherein:
- each R1 is independently selected from the group consisting of a side chain of a natural amino acid and a side chain of an unnatural amino acid, wherein the natural amino acid and the unnatural amino acid is either in the D or L form;
- R2 and R3 are each independently selected from the group consisting of —H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkyloxy, C1-C6 alkoxyalkyl, aryl, aryl-(C1-C6 alkylene)-, 3- to 7-membered carbocycle, 3- to 7-membered heterocycle, hydroxy-C1-C6-alkyl, and C1-C6-alkoxy-C1-C6-alkyl, wherein the alkyl, alkenyl, alkynyl, alkyloxy, alkoxyalkyl, aryl, carbocycle, and heterocycle, groups are each optionally substituted, wherein R2 and R3 are not both H;
- and either R2 or R3, or both R2 and R3 comprise a radionuclide selected from the group consisting of 11C, 13N, 15O, 18F, 75Br, 124I, 125I and 131I;
- and
- W is
- where p is an integer between 0 and 15;
- v is 0, 1, 2, or 3;
- m is 0, 1 or 2;
- each R4 is independently selected from the group consisting of —H, C1-C6 alkyl, C2-C6 alkenyl, and C2-C6 alkynyl, wherein the alkyl, alkenyl, and alkynyl groups are each optionally substituted;
- R5 is selected from the group consisting of —H, C1-C6 alkyl, C2-C6 alkenyl, and C2-C6 alkynyl, wherein the alkyl, alkenyl and alkynyl groups are each optionally substituted and wherein the configuration of the chiral center that is substituted with the R5 substituent may be R or S or mixtures thereof;
- and
- each R8 is independently selected from the group consisting of a side chain of a natural amino acid and a side chain of an unnatural amino acid, wherein the natural amino acid and the unnatural amino acid is either in the D or L form.
10 more elements
A cyclopeptide of formula III:
- wherein:
- R1 is selected from the group consisting of a side chain of a natural amino acid and a side chain of an unnatural amino acid, wherein the natural amino acid and the unnatural amino acid is either in the D or L form;
- R2 and R3 are each independently selected from the group consisting of —H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkyloxy, C1-C6 alkoxyalkyl, aryl, aryl-(C1-C6 alkylene)-, 3- to 7-membered carbocycle, 3- to 7-membered heterocycle, hydroxy-C1-C6-alkyl, and C1-C6-alkoxy-C1-C6-alkyl, wherein the alkyl, alkenyl, alkynyl, alkyloxy, alkoxyalkyl, aryl, carbocycle, and heterocycle, groups are each optionally substituted;
- wherein R2 and R3 are not both H;
- and either R2 or R3, or both R2 and R3 comprise a radionuclide selected from the group consisting of positron or gamma emitters;
- R8 is selected from the group consisting of a side chain of a natural amino acid and a side chain of an unnatural amino acid, wherein the natural amino acid and the unnatural amino acid is either in the D or L form;
- and
- X is a linker comprising a hydrophilic moiety selected from the group consisting of hydroxyl, carbonyl, amide (—C(O)NH—), sulfonamide, sulfonate, phosphate, polar amino acid moiety, PEG moiety, sugar mimetic and sugar moiety, or a combination thereof.
5 more elements
A radiolabeled cyclopeptide of formula IV:
- wherein:
- R5 is selected from the group consisting of H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkyloxy, aryl, —(C1-C6 alkylene)-aryl, 3- to 7-membered carbocycle, 3- to 7-membered heterocycle, hydroxy-C1-C6-alkyl, and C1-C6-alkoxy-C1-C6-alkyl;
- wherein the alkyl, alkenyl, alkynyl, alkyloxy, aryl, carbocycle and heterocycle groups are each optionally substituted;
- R8 is selected from the group consisting of a side chain of a natural amino acid and a side chain of an unnatural amino acid, wherein the natural amino acid and the unnatural amino acid is either in the D or L form;
- wherein the chiral centers attached to bonds are R or S or mixtures thereof;
- m is 0, 1, 2, 3 or 4;
- and
- n is 1, 2, 3, 4 or 5.
5 more elements
A radiolabeled cyclopeptide selected from the group consisting of:
- wherein each R8 is selected from the group consisting of a side chain of a natural amino acid and a side chain of an unnatural amino acid, wherein the natural amino acid and the unnatural amino acid is either in the D or L form.
A pharmaceutical composition comprising a radiolabeled cyclopeptide of formula I:
- wherein:
- R1 is selected from the group consisting of a side chain of a natural amino acid and a side chain of an unnatural amino acid, wherein the natural amino acid and the unnatural amino acid is either in the D or L form;
- R2 and R3 are each independently selected from the group consisting of —H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkyloxy, C1-C6 alkoxyalkyl, aryl, aryl-(C1-C6 alkylene)-, 3- to 7-membered carbocycle, 3- to 7-membered heterocycle, hydroxy-C1-C6-alkyl, and C1-C6-alkoxy-C1-C6-alkyl, wherein the alkyl, alkenyl, alkynyl, alkyloxy, alkoxyalkyl, aryl, carbocycle, and heterocycle, groups are each optionally substituted;
- R7 is absent or is selected from the group consisting of H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, aryl, aryl-(C1-C6 alkylene)-, a 3- to 7-membered carbocycle, and a 3- to 7-membered heterocycle, wherein the alkyl, alkenyl, alkynyl, aryl-alkylene, carbocycle and heterocycle groups are each optionally substituted;
- wherein R2, R3 and R7 are not all H;
- R8 is selected from the group consisting of a side chain of a natural amino acid and a side chain of an unnatural amino acid, wherein the natural amino acid and the unnatural amino acid is either in the D or L form;
- X is a 5 or 6-membered heterocycle or a linker comprising a hydrophilic moiety selected from the group consisting of hydroxyl, carbonyl, amide (—C(O)NH—), sulfonamide, sulfonate, phosphate, polar amino acid moiety, PEG moiety, sugar mimetic, and sugar moiety, or a combination thereof;
- Y is a 5 or 6-membered heterocycle, or a linker comprising a hydrophilic moiety selected from the group consisting of hydroxyl, carbonyl, sulfonamide, sulfonate, phosphate, polar amino acid moiety, PEG moiety, sugar mimetic, and sugar moiety;
- where at least one of X and Y, but not both X and Y is a 5 or 6-membered heterocycle;
- and
- w is 1, 2, 3, 4, or 5;
- wherein any one of X, Y, R2, R3, and R7 comprises a radionuclide selected from the group consisting of positron or gamma emitters;
- and a pharmaceutically acceptable carrier.
10 more elements
A pharmaceutical composition comprising a radiolabeled cyclopeptide of formula II or formula III:
- wherein:
- each R1 is independently selected from the group consisting of a side chain of a natural amino acid and a side chain of an unnatural amino acid, wherein the natural amino acid and the unnatural amino acid is either in the D or L form;
- R2 and R3 are each independently selected from the group consisting of —H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkyloxy, C1-C6 alkoxyalkyl, aryl, aryl-(C1-C6 alkylene)-, 3- to 7-membered carbocycle, 3- to 7-membered heterocycle, hydroxy-C1-C6-alkyl, and C1-C6-alkoxy-C1-C6-alkyl, wherein the alkyl, alkenyl, alkynyl, alkyloxy, alkoxyalkyl, aryl, carbocycle, and heterocycle, groups are each optionally substituted, wherein R2 and R3 are not both H;
- and either R2 or R3, or both R2 and R3 comprise a radionuclide selected from the group consisting of 11C, 13N, 15O, 18F, 61Cu, 62Cu, 64Cu, 67Cu, 68Ga, 124I, 125I, 131I, 99Tc, 75Br, 153Gd and 32P;
- each of X and W is selected from the group consisting of:
- where each R4 is independently selected from the group consisting of —H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkyloxy, aryl, aryl-(C1-C6 alkylene)-, 3- to 7-membered carbocycle, 3- to 7-membered heterocycle, hydroxy-C1-C6-alkyl, C1-C6-alkoxy-C1-C6-alkyl, and a PEG moiety, wherein the alkyl, alkenyl, alkynyl, alkoxy, aryl, carbocycle, and heterocycle groups are each optionally substituted;
- R5 is selected from the group consisting of —H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkyloxy, aryl, aryl-(C1-C6 alkylene)-, 3- to 7-membered carbocycle, 3- to 7-membered heterocycle, hydroxy-C1-C6-alkyl, and C1-C6-alkoxy-C1-C6-alkyl, wherein the alkyl, alkenyl, alkynyl, alkyloxy, aryl, carbocycle, and heterocycle, groups are each optionally substituted;
- each R8 is independently selected from the group consisting of a side chain of a natural amino acid and a side chain of an unnatural amino acid, wherein the natural amino acid and the unnatural amino acid is either in the D or L form;
- v is 0, 1, 2, 3, or 4;
- m is 0, 1, 2, 3 or 4;
- and
- p is an integer between 1 and 25;
- wherein the configuration of the chiral centers may be R or S or mixtures thereof;
- and a pharmaceutically acceptable carrier.
11 more elements
A pharmaceutical composition comprising a radiolabeled cyclopeptide selected from the group consisting of:
- wherein:
- each R8 is independently selected from the group consisting of a side chain of a natural amino acid and a side chain of an unnatural amino acid, wherein the natural amino acid and the unnatural amino acid is either in the D or L form;
- and a pharmaceutically acceptable carrier.
A method of monitoring the level of integrin αvβ3 or visualizing integrin αvβ3 expression within a body of a patient, the method comprising:
- (a) administering to the patient a radiolabeled cyclopeptide;
- and (b) employing a nuclear imaging technique selected from the group consisting of positron emission tomography (PET) and single photon emission computed tomography (SPECT) for monitoring or visualizing a distribution of the radiolabeled cyclopeptide within the body or within a portion thereof;
- wherein the radiolabeled cyclopeptide is of formula I:
- wherein
- R1 is selected from the group consisting of a side chain of a natural amino acid and a side chain of an unnatural amino acid, wherein the natural amino acid and the unnatural amino acid is either in the D or L form;
- R2 and R3 are each independently selected from the group consisting of —H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkyloxy, C1-C6 alkoxyalkyl, aryl, aryl-(C1-C6 alkylene)-, 3- to 7-membered carbocycle, 3- to 7-membered heterocycle, hydroxy-C1-C6-alkyl, and C1-C6-alkoxy-C1-C6-alkyl, wherein the alkyl, alkenyl, alkynyl, alkyloxy, alkoxyalkyl, aryl, carbocycle, and heterocycle, groups are each optionally substituted;
- R7 is absent or is selected from the group consisting of H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, aryl, aryl-(C1-C6 alkylene)-, a 3- to 7-membered carbocycle, and a 3- to 7-membered heterocycle, wherein the alkyl, alkenyl, alkynyl, aryl-alkylene, carbocycle and heterocycle groups are each optionally substituted;
- wherein R2, R3 and R7 are not all H;
- R8 is selected from the group consisting of a side chain of a natural amino acid and a side chain of an unnatural amino acid, wherein the natural amino acid and the unnatural amino acid is either in the D or L form;
- X is a 5 or 6-membered heterocycle or a linker comprising a hydrophilic moiety selected from the group consisting of hydroxyl, carbonyl, amide (—C(O)NH—), sulfonamide, sulfonate, phosphate, polar amino acid moiety, PEG moiety, sugar mimetic, and sugar moiety, or a combination thereof;
- Y is a 5 or 6-membered heterocycle, or a linker comprising a hydrophilic moiety selected from the group consisting of hydroxyl, carbonyl, sulfonamide, sulfonate, phosphate, polar amino acid moiety, PEG moiety, sugar mimetic, and sugar moiety;
- where at least one of X and Y, but not both X and Y is a 5 or 6-membered heterocycle;
- and
- w is 1, 2, 3, 4, or 5;
- wherein any one of X, Y, R2, R3, and R7 comprises a radionuclide selected from the group consisting of positron or gamma emitters.
12 more elements
A method of monitoring the level of integrin αvβ3 or visualizing integrin αvβ3 expression within a body of a patient, the method comprising:
- (a) administering to the patient a radiolabeled cyclopeptide;
- and (b) employing a nuclear imaging technique selected from the group consisting of positron emission tomography (PET) and single photon emission computed tomography (SPECT) for monitoring or visualizing a distribution of the radiolabeled cyclopeptide within the body or within a portion thereof;
- wherein the radiolabeled cyclopeptide is of formula II or formula III:
- wherein
- each R1 is independently selected from the group consisting of a side chain of a natural amino acid and a side chain of an unnatural amino acid, wherein the natural amino acid and the unnatural amino acid is either in the D or L form;
- R2 and R3 are each independently selected from the group consisting of —H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkyloxy, C1-C6 alkoxyalkyl, aryl, aryl-(C1-C6 alkylene)-, 3- to 7-membered carbocycle, 3- to 7-membered heterocycle, hydroxy-C1-C6-alkyl, and C1-C6-alkoxy-C1-C6-alkyl, wherein the alkyl, alkenyl, alkynyl, alkyloxy, alkoxyalkyl, aryl, carbocycle, and heterocycle, groups are each optionally substituted, wherein R2 and R3 are not both H;
- and either R2 or R3, or both R2 and R3 comprise a radionuclide selected from the group consisting of 11C, 13N, 15O, 18F, 61Cu, 62Cu, 64Cu, 67Cu, 68Ga, 124I, 125I, 131I, 99Tc, 75Br, 153Gd and 32P;
- each of X and W is selected from the group consisting of:
- where each R4 is independently selected from the group consisting of —H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkyloxy, aryl, aryl-(C1-C6 alkylene)-, 3- to 7-membered carbocycle, 3- to 7-membered heterocycle, hydroxy-C1-C6-alkyl, C1-C6-alkoxy-C1-C6-alkyl, and a PEG moiety, wherein the alkyl, alkenyl, alkynyl, alkoxy, aryl, carbocycle, and heterocycle groups are each optionally substituted;
- R5 is selected from the group consisting of —H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkyloxy, aryl, aryl-(C1-C6 alkylene)-, 3- to 7-membered carbocycle, 3- to 7-membered heterocycle, hydroxy-C1-C6-alkyl, and C1-C6-alkoxy-C1-C6-alkyl, wherein the alkyl, alkenyl, alkynyl, alkyloxy, aryl, carbocycle, and heterocycle, groups are each optionally substituted;
- each R8 is independently selected from the group consisting of a side chain of a natural amino acid and a side chain of an unnatural amino acid, wherein the natural amino acid and the unnatural amino acid is either in the D or L form;
- wherein the configuration of the chiral centers may be R or S or mixtures thereof;
- v is 0, 1, 2, 3, or 4;
- m is 0, 1, 2, 3 or 4;
- and
- p is an integer between 1 and 25.
13 more elements
A method of monitoring the level of integrin αvβ3 or visualizing integrin αvβ3 expression within a body of a patient, the method comprising:
- (a) administering to the patient a radiolabeled cyclopeptide;
- and (b) employing a nuclear imaging technique selected from the group consisting of positron emission tomography (PET) and single photon emission computed tomography (SPECT) for monitoring or visualizing a distribution of the radiolabeled cyclopeptide within the body or within a portion thereof;
- wherein the radiolabeled cyclopeptide is selected from the group consisting of:
- wherein:
- each R8 is independently selected from the group consisting of a side chain of a natural amino acid and a side chain of an unnatural amino acid, wherein the natural amino acid and the unnatural amino acid is either in the D or L form.
2 more elements
A method for imaging of blood vessel growth in solid tumors based on expression of integrin αvβ3 within the body of a patient, the method comprising:
- (a) administering to the patient a radiolabeled cyclopeptide;
- (b) employing a nuclear imaging technique selected from the group consisting of positron emission tomography (PET) and single photon emission computed tomography (SPECT) for imaging a distribution of the radiolabeled cyclopeptide within the body or within a portion thereof;
- and c) correlating the distribution of the radiolabeled cyclopeptide to the growth of blood vessels in solid tumors, wherein the radiolabeled cyclopeptide is of formula I:
- wherein:
- R1 is selected from the group consisting of a side chain of a natural amino acid and a side chain of an unnatural amino acid, wherein the natural amino acid and the unnatural amino acid is either in the D or L form;
- R2 and R3 are each independently selected from the group consisting of —H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkyloxy, C1-C6 alkoxyalkyl, aryl, aryl-(C1-C6 alkylene)-, 3- to 7-membered carbocycle, 3- to 7-membered heterocycle, hydroxy-C1-C6-alkyl, and C1-C6-alkoxy-C1-C6-alkyl, wherein the alkyl, alkenyl, alkynyl, alkyloxy, alkoxyalkyl, aryl, carbocycle, and heterocycle, groups are each optionally substituted;
- R7 is absent or is selected from the group consisting of H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, aryl, aryl-(C1-C6 alkylene)-, a 3- to 7-membered carbocycle, and a 3- to 7-membered heterocycle, wherein the alkyl, alkenyl, alkynyl, aryl-alkylene, carbocycle and heterocycle groups are each optionally substituted;
- wherein R2, R3 and R7 are not all H;
- R8 is selected from the group consisting of a side chain of a natural amino acid and a side chain of an unnatural amino acid, wherein the natural amino acid and the unnatural amino acid is either in the D or L form;
- X is a 5 or 6-membered heterocycle or a linker comprising a hydrophilic moiety selected from the group consisting of hydroxyl, carbonyl, amide (—C(O)NH—), sulfonamide, sulfonate, phosphate, polar amino acid moiety, PEG moiety, sugar mimetic, and sugar moiety, or a combination thereof;
- Y is a 5 or 6-membered heterocycle, or a linker comprising a hydrophilic moiety selected from the group consisting of hydroxyl, carbonyl, sulfonamide, sulfonate, phosphate, polar amino acid moiety, PEG moiety, sugar mimetic, and sugar moiety;
- where at least one of X and Y, but not both X and Y is a 5 or 6-membered heterocycle;
- and
- w is 1, 2, 3, 4, or 5;
- wherein any one of X, Y, R2, R3, and R7 comprises a radionuclide selected from the group consisting of positron or gamma emitters.
12 more elements
A method for imaging of blood vessel growth in solid tumors based on expression of integrin αvβ3 within the body of a patient, the method comprising:
- (a) administering to the patient a radiolabeled cyclopeptide;
- (b) employing a nuclear imaging technique selected from the group consisting of positron emission tomography (PET) and single photon emission computed tomography (SPECT) for imaging a distribution of the radiolabeled cyclopeptide within the body or within a portion thereof;
- and c) correlating the distribution of the radiolabeled cyclopeptide to the growth of blood vessels in solid tumors, wherein the radiolabeled cyclopeptide is of formula II or formula III:
- wherein:
- each R1 is independently selected from the group consisting of a side chain of a natural amino acid and a side chain of an unnatural amino acid, wherein the natural amino acid and the unnatural amino acid is either in the D or L form;
- R2 and R3 are each independently selected from the group consisting of —H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkyloxy, C1-C6 alkoxyalkyl, aryl, aryl-(C1-C6 alkylene)-, 3- to 7-membered carbocycle, 3- to 7-membered heterocycle, hydroxy-C1-C6-alkyl, and C1-C6-alkoxy-C1-C6-alkyl, wherein the alkyl, alkenyl, alkynyl, alkyloxy, alkoxyalkyl, aryl, carbocycle, and heterocycle, groups are each optionally substituted, wherein R2 and R3 are not both H;
- and either R2 or R3, or both R2 and R3 comprise a radionuclide selected from the group consisting of 11C, 13N, 15O, 18F, 61Cu, 62Cu, 64Cu, 67Cu, 68Ga, 124I, 125I, 131I, 99Tc, 75Br, 153Gd and 32P;
- each of X and W is selected from the group consisting of:
- where each R4 is independently selected from the group consisting of —H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkyloxy, aryl, aryl-(C1-C6 alkylene)-, 3- to 7-membered carbocycle, 3- to 7-membered heterocycle, hydroxy-C1-C6-alkyl, C1-C6-alkoxy-C1-C6-alkyl, and a PEG moiety, wherein the alkyl, alkenyl, alkynyl, alkoxy, aryl, carbocycle, and heterocycle groups are each optionally substituted;
- R5 is selected from the group consisting of —H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkyloxy, aryl, aryl-(C1-C6 alkylene)-, 3- to 7-membered carbocycle, 3- to 7-membered heterocycle, hydroxy-C1-C6-alkyl, and C1-C6-alkoxy-C1-C6-alkyl, wherein the alkyl, alkenyl, alkynyl, alkyloxy, aryl, carbocycle, and heterocycle, groups are each optionally substituted;
- each R8 is independently selected from the group consisting of a side chain of a natural amino acid and a side chain of an unnatural amino acid, wherein the natural amino acid and the unnatural amino acid is either in the D or L form;
- wherein the configuration of the chiral centers may be R or S or mixtures thereof;
- v is 0, 1, 2, 3, or 4;
- m is 0, 1, 2, 3 or 4;
- and
- p is an integer between 1 and 25.
13 more elements
A method for imaging of blood vessel growth in solid tumors based on expression of integrin αvβ3 within the body of a patient, the method comprising:
- (a) administering to the patient a radiolabeled cyclopeptide;
- (b) employing a nuclear imaging technique selected from the group consisting of positron emission tomography (PET) and single photon emission computed tomography (SPECT) for imaging a distribution of the radiolabeled cyclopeptide within the body or within a portion thereof;
- and c) correlating the distribution of the radiolabeled cyclopeptide to the growth of blood vessels in solid tumors, wherein the radiolabeled cyclopeptide is selected from the group consisting of:
- wherein:
- each R8 is independently selected from the group consisting of a side chain of a natural amino acid and a side chain of an unnatural amino acid, wherein the natural amino acid and the unnatural amino acid is either in the D or L form.
2 more elements
Dependencies are inferred from the claim text.