Compositions and methods for assessing eye vasculature

Abstract

The present disclosure relates to compositions and methods for assessing blood vessels and organs of the body, more specifically to methods for assessing the vasculature of the eye.

1 - 29 . (canceled) 
     
     
         30 . A method of assessing the location of a disease or an injury in a subject's vasculature, comprising the steps of:
 a. administering an effective amount of a compound of structural Formula I   
       
         
           
           
               
               
           
         
          or a salt thereof; wherein
 X 1  and X 2  are independently chosen from —CO(AA), —CN, —CO 2 R 1 , —CONR 2 R 3 , —COR 4 , —NO 2 , —SOR 35 , —SO 2 R 6 , —SO 2 OR 7  and —PO 3 R 8 R 9 ; 
 Y 1  and Y 2  are independently chosen from OR 10 , —SR 11 , —NR 12 R 13 , —N(R 14 )COR 15 , —CONH(PS): —P(R 16 ) 2 , —P(OR 17 ) 2  and 
 
       
       
         
           
           
               
               
           
         
          each Z 1  is independently chosen from a bond, —CR 18 R 19 , —O—, —NR 20 —, —NCOR 21 —, —S—, —SO—, and —SO 2 —;
 each R 1  to R 21  are independently chosen from hydrogen, C 1 -C 10  alkyl optionally substituted with hydroxyl and carboxylic acid, C 3 -C 6  polyhydroxylated alkyl, C 5 -C 10  aryl, C 5 -C 10  heteroaryl, C 3 -C 5  heterocycloalkyl optionally substituted with C(O), —(CH 2 ) a CO 2 H optionally substituted with C 5 -C 10  heteroaryl, —(CH 2 ) a CONR 30 R 31 , —(CH 2 ) a NHSO 3   − , —(CH 2 ) a NHSO 3 H, —(CH 2 ) a OH, —(CH 2 ) a OPO 3   = , —(CH 2 ) a OPO 3 H 2 , —(CH 2 ) a OPO 3 H − , —(CH 2 ) a OR 22 , —(CH 2 ) a OSO 3   − , —(CH 2 ) a OSO 3 H, —(CH 2 ) a PO 3   = , —(CH 2 ) a PO 3 H 2 , —(CH 2 ) a PO 3 H − , —(CH 2 ) a SO 3   − , —(CH 2 ) a SO 3 H, —(CH 2 ) d CO(CH 2 CH 2 O) c R 23 , —(CH 2 ) d (CH 2 CH 2 O) c R 24 , —(CHCO 2 H) a CO 2 H, —CH 2 (CHNH 2 ) a CH 2 NR 25 R 26 , —CH 2 (CHOH) a CO 2 H, —CH 2 (CHOH) a R 27 , —CH[(CH 2 ) b NH 2 ] a CH 2  OH, —CH[(CH 2 ) b NH 2 ] a CO 2 H, and —(CH 2 ) a NR 28 R 29 ; 
 each R 22  to R 31  are independently chosen from hydrogen, C 1 -C 10  alkyl, and C 1 - 5 -dicarboxylic acid; 
 R 35  is chosen from C 1 -C 10  alkyl optionally substituted with hydroxyl and carboxylic acid, C 3 -C 6  polyhydroxylated alkyl, C 5 -C 10  aryl, C 5 -C 10  heteroaryl, C 3 -C 5  heterocycloalkyl optionally substituted with C(O), —(CH 2 ) a CO 2 H optionally substituted with C 5 -C 10  heteroaryl, —(CH 2 ) a CONR 30 R 31 , —(CH 2 ) a NHSO 3   − , —(CH 2 ) a NHSO 3 H, —(CH 2 ) a OH, —(CH 2 ) a OPO = , —(CH 2 ) a OPO 3 H 2 , —(CH 2 ) a OPO 3 H − , —(CH 2 ) a OR 22 , —(CH 2 ) a OSO 3   − , —(CH 2 ) a OSO 3 H, —(CH 2 ) a PO 3   − , —(CH 2 ) a PO 3 H 2 , —(CH 2 ) a PO 3 H − , —(CH 2 ) a SO 3   − , —(CH 2 ) a SO 3 H, —(CH 2 ) d CO(CH 2 CH 2 O) c R 23 , —(CH 2 ) d (CH 2 CH 2 O) c R 24 , —(CHCO 2 H) a CO 2 H, —CH 2 (CHNH 2 ) a CH 2 NR 25 R 26 , —CH 2 (CHOH) a CO 2 H, —CH 2  (CHOH) a R 27 , —CH[(CH 2 ) b NH 2 ] a CH 2— OH, CH[(CH 2 ) b NH 2 ] a CO 2 H, and —(CH 2 ) a NR 28 R 29 ; 
 (AA) is a polypeptide chain comprising one or more natural or unnatural amino acids linked together by peptide bonds; 
 (PS) is a sulfated or non-sulfated polysaccharide chain comprising one or more monosaccharide units connected by glycosidic linkages; and 
 each ‘a’, and ‘d’ are independently chosen from 0 to 10, ‘c’ is chosen from 1 to 100 and each of ‘m’ and ‘n’ independently is an integer from 1 to 3; 
 
         b. irradiating the subject's vasculature with non-ionizing radiation, wherein the radiation causes the compound to fluoresce; 
         c. detecting the fluorescence of the compound in the subject's vasculature; and 
         d. assessing the location of disease or injury in the subject's vasculature, based on the detected fluorescence. 
       
     
     
         31 . The method of  claim 30 , wherein the composition is administered intravenously. 
     
     
         32 . The method of  claim 30 , wherein the non-ionizing radiation has a wavelength of at least 350 nm. 
     
     
         33 . The method of  claim 30 , wherein the detected fluorescence of the compound in the subject's vasculature is measured over time. 
     
     
         34 . The method of  claim 30 , wherein the subject's pulmonary and cardiac vasculature is assessed. 
     
     
         35 . The method of  claim 34 , wherein assessing the subject's pulmonary and cardiac vasculature comprises identifying abnormalities chosen from stenosis, occlusions, aneurysms, and combinations thereof. 
     
     
         36 . The method of  claim 35 , wherein assessing the subject's pulmonary and cardiac vasculature comprises comparing the detected fluorescence in the subject's pulmonary and cardiac vasculature to that of normal pulmonary and cardiac vasculature under similar conditions. 
     
     
         37 . The method of  claim 30 , wherein the subject's eye vasculature is assessed. 
     
     
         38 . The method of  claim 37 , wherein assessing the subject's eye vasculature comprises identifying ocular abnormalities. 
     
     
         39 . The method of  claim 38 , wherein the ocular abnormalities are chosen from blood vessel architecture, ischemic spots, choroidal infarcts, Elschnig's spots, exudates, hemorrhages, and combinations thereof 
     
     
         40 . The method of  claim 38 , wherein the ocular abnormalities are chosen from vessel crossovers, vessel tortuosity, evidence of exudates, and combinations thereof. 
     
     
         41 . The method of  claim 38 , wherein assessing the subject's eye vasculature comprises comparing the detected fluorescence in the subject's eye to that of a normal eye under similar conditions. 
     
     
         42 . The method of  claim 30 , wherein said amino acids are chosen from α-amino acids, β-amino acids, and γ-amino acids.