Tricarbonyl complexes with tridentate chelators for myocardium imaging
View Patent ↗Chelators of the formulae (I), (II) and (III) and tricarbonyl complexes of radioisotopes of Tc and Re bound to them, for use in myocardial imaging.
1. A method of myocardial imaging, the method comprising,
(a) administering to a subject a radioisotopic tricarbonyl complex with a tridentate chelator chosen from a compound comprising Formula (I), (II), or (III):
wherein,
n is an integer selected from 1 or 2, and
at least one of R 1 , R 2 , R 3 , and R 4 is a linear or macrocyclic ether group of the type —R x —O—R Y or [(CH 2 ) x O] y (CH 2 ) z (x=2-3, y=3-8, z=2-5), respectively,
and each of the other three R groups is independently hydrogen; a linear or branched, saturated or unsaturated C 1 to C 9 alkyl; a saturated or unsaturated carbocyclic group; a saturated or unsaturated heterocyclic or heteroaliphatic group with one or more atoms selected from O, N and S, wherein said carbocyclics, heterocyclics and heteroaliphatics are optionally substituted by one or more linear or branched, saturated or unsaturated C 1 to C 9 alkyls; an ether group —R x —O—R Y or [(CH 2 ) x O] y (CH 2 ) z (x=2-3, y=3-8, z=2-5),
wherein R x and R Y are independently linear or branched, saturated or unsaturated C 1 to C 9 alkyl, or saturated or unsaturated carbocyclics, any of which alkyl and/or carbocyclic groups may be substituted or unsubstituted,
provided that when the tridentate chelator is of the type of formula (I), when R 1 is —R x —O—R Y wherein R Y is substituted, and R 2 , R 3 , and R 4 are each hydrogen, R Y is not substituted apically by a further tris(pyrazolyl)methane moiety; and when R 1 is —R x —O—R Y and R 2 , R 3 and R 4 are each hydrogen, R 1 cannot be —CH 2 —O—CH 2 -(p- t Bu-C 6 H 4 ); and
(b) evaluating the biodistribution of the radioisotopic tricarbonyl complex.
2. The method of claim 1 , wherein the biodistribution of the radioisotopic tricarbonyl complex is evaluated by SPECT or planar scintography.
3. The method of claim 1 , wherein administration is intravenous.
4. The method of claim 1 , wherein the radioisotopic tricarbonyl complex is selected from a Tc or Re radioisotopic tricarbonyl complex.
5. A method of myocardial imaging, the method comprising,
(a) administering to a subject a radioisotopic tricarbonyl complex with a tridentate chelator chosen from a compound comprising Formula (I):
wherein,
at least one of R 1 , R 2 , R 3 , and R 4 is a linear or macrocyclic ether group of the type —R x —O—R Y or [(CH 2 ) x O] y (CH 2 ) z (x=2-3, y=3-8, z=2-5), respectively,
and each of the other three R groups is independently hydrogen; a linear or branched, saturated or unsaturated C 1 to C 9 alkyl; a saturated or unsaturated carbocyclic group; a saturated or unsaturated heterocyclic or heteroaliphatic group with one or more atoms selected from O, N and S, wherein said carbocyclics, heterocyclics and heteroaliphatics are optionally substituted by one or more linear or branched, saturated or unsaturated C 1 to C 9 alkyls; an ether group —R x —O—R Y or [(CH 2 ) x O] y (CH 2 ) z (x=2-3, y=3-8, z=2-5),
wherein R x and R Y are independently linear or branched, saturated or unsaturated C 1 to C 9 alkyl, or saturated or unsaturated carbocyclics, any of which alkyl and/or carbocyclic groups may be substituted or unsubstituted,
provided that when R 1 is —R x —O—R Y wherein R Y is substituted, and R 2 , R 3 , and R 4 are each H, R Y is not substituted apically by a further tris(pyrazolyl)methane moiety; and when R 1 is —R x —O—R Y and R 2 , R 3 and R 4 are each H, R 1 cannot be —CH 2 —O—CH 2 -(p- t Bu-C 6 H 4 ); and
(b) evaluating the biodistribution of the radioisotopic tricarbonyl complex.
6. The method of claim 5 , wherein the biodistribution of the radioisotopic tricarbonyl complex is evaluated by SPECT or planar scintography.
7. The method of claim 5 , wherein administration is intravenous.
8. The method of claim 5 , wherein the radioisotopic tricarbonyl complex is selected from a Tc or Re radioisotopic tricarbonyl complex.
9. The method of claim 5 , wherein R1 is hydrogen; R2 and R4 are C 1 to C 3 alkyl; and R3 is the ether group —R x —O—R Y , where R x and R Y are linear C 1 to C 9 alkyl.
10. The method of claim 5 , wherein R1 and R3 are hydrogen, and R2 and R4 are the ether group —R x —O—R Y , where R x and R Y are linear C 1 to C 9 alkyl.
11. The method of claim 5 , wherein R1 is H and R2, R3, and R4 are the ether group —R x —O—R Y , where R x and R Y are linear C 1 to C 9 alkyl.
12. The method of claim 5 , wherein R1, R2, and R4 are hydrogen, and R3 is the ether group —R x —O—R Y , where R x and R Y are linear C 1 to C 9 alkyl.
13. The method of claim 5 , wherein R1 is the ether group —R x —O—R Y , where R x and R Y are linear C 1 to C 9 alkyl, and R2, R3, and R4 are hydrogen.
14. A method of myocardial imaging, the method comprising,
(a) administering to a subject a radioisotopic tricarbonyl complex with a tridentate chelator chosen from a compound comprising Formula (II):
wherein,
n is an integer selected from 1 or 2, and
at least one of R 1 , R 2 , R 3 , and R 4 is a linear or macrocyclic ether group of the type —R x —O—R Y or [(CH 2 ) x O] y (CH 2 ) z =2-3, y=3-8, z=2-5), respectively,
and each of the other three R groups is independently hydrogen; a linear or branched, saturated or unsaturated C 1 to C 9 alkyl; a saturated or unsaturated carbocyclic group; a saturated or unsaturated heterocyclic or heteroaliphatic group with one or more atoms selected from O, N and S, wherein said carbocyclics, heterocyclics and heteroaliphatics are optionally substituted by one or more linear or branched, saturated or unsaturated C 1 to C 9 alkyls; an ether group —R x —O—R Y or [(CH 2 ) x O] y (CH 2 ) z (x=2-3, y=3-8, z=2-5),
wherein R x and R Y are independently linear or branched, saturated or unsaturated C 1 to C 9 alkyl, or saturated or unsaturated carbocyclics, any of which alkyl and/or carbocyclic groups may be substituted or unsubstituted; and
(b) evaluating the biodistribution of the radioisotopic tricarbonyl complex.
15. The method of claim 14 , wherein the biodistribution of the radioisotopic tricarbonyl complex is evaluated by SPECT or planar scintography.
16. The method of claim 14 , wherein the radioisotopic tricarbonyl complex is selected from a Tc or Re radioisotopic tricarbonyl complex.
17. The method of claim 14 , wherein administration is intravenous.
18. The method of claim 14 , wherein n is equal to 1; R1 is the ether group —R x —O—R Y , where R x and R Y are linear C 1 to C 9 alkyl; and R2, R3, and R4 are hydrogen.
19. A method of myocardial imaging, the method comprising,
(a) administering to a subject a radioisotopic tricarbonyl complex with a tridentate chelator chosen from a compound comprising Formula (III):
wherein,
n is an integer selected from 1 or 2, and
at least one of R 1 , R 2 , R 3 , and R 4 is a linear or macrocyclic ether group of the type —R x —O—R Y or [(CH 2 ) x O] y (CH 2 ) z (x=2-3, y=3-8, z=2-5), respectively,
and each of the other three R groups is independently hydrogen; a linear or branched, saturated or unsaturated C 1 to C 9 alkyl; a saturated or unsaturated carbocyclic group; a saturated or unsaturated heterocyclic or heteroaliphatic group with one or more atoms selected from O, N and S, wherein said carbocyclics, heterocyclics and heteroaliphatics are optionally substituted by one or more linear or branched, saturated or unsaturated C 1 to C 9 alkyls; an ether group —R x —O—R Y or [(CH 2 ) x O] y (CH 2 ) z (x=2-3, y=3-8, z=2-5),
wherein R x and R Y are independently linear or branched, saturated or unsaturated C 1 to C 9 alkyl, or saturated or unsaturated carbocyclics, any of which alkyl and/or carbocyclic groups may be substituted or unsubstituted, and
(b) evaluating the biodistribution of the radioisotopic tricarbonyl complex.
20. The method of claim 19 , wherein the biodistribution of the radioisotopic tricarbonyl complex is evaluated by SPECT or planar scintography.
21. The method of claim 19 , wherein the radioisotopic tricarbonyl complex is selected from a Tc or Re radioisotopic tricarbonyl complex.
22. The method of claim 19 , wherein administration is intravenous.
23. The method of claim 19 , wherein n is equal to 2; R1, R2, and R4 are the ether group —R x —O—R Y , where R x and R Y are linear C 1 to C 9 alkyl; and R 3 is hydrogen.