Patent ID: 8486372
Filing Date: 2013-07-16
Classification: A61K,A61P,C07K

Abstract:
1. A method for imaging of blood vessel growth in solid tumors based on expression of integrin α v β 3 within the body of a patient, the method comprising: (a) administering to the patient a radiolabeled cycloazapeptide; (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 cycloazapeptide within the body or within a portion thereof; and (c) correlating the distribution of the radiolabeled cycloazapeptide to the growth of blood vessels in solid tumors, wherein the radiolabeled cycloazapeptide is of formula II: wherein: each R 1 is hydrogen or 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; R 2 and R 3 are each independently selected from the group consisting of —H, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 alkyloxy, C 1 -C 6 alkoxyalkyl, aryl, aryl-(C 1 -C 6 alkylene)-, 3- to 7-membered carbocycle, 3- to 7-membered heterocycle, hydroxy-C 1 -C 6 -alkyl and C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl, wherein the alkyl, alkenyl, alkynyl, alkyloxy, alkoxyalkyl, aryl, carbocycle and heterocycle, groups are each optionally substituted, wherein R 2 and R 3 are not both H; and either R 2 or R 3 , or both R 2 and R 3 comprise a radionuclide selected from the group consisting of 11 C, 13 N, 15 O, 18 F, 75 Br, 124 I, 125 I and 131 I; 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 R 4 is independently selected from the group consisting of —H, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, and C 2 -C 6 alkynyl, wherein the alkyl, alkenyl and alkynyl groups are each optionally substituted; R 5 is selected from the group consisting of —H, C 1 -C 6 alkyl, C 2 -C 6 alkenyl and C 2 -C 6 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 R 5 substituent is R or S or mixtures thereof; or a pharmaceutically acceptable salt thereof, optionally in the form of a single stereoisomer or mixture of stereoisomers thereof.