COMPOSITIONS COMPRISING ASCORBIC ACID AND AN IMAGING AGENT AND RELATED METHODS
The present invention is generally directed towards compositions comprising ascorbic acid or ascorbate salt and an imaging agent, and related methods. In some embodiments, the imaging agent comprises pyridaben or a pyridaben analog attached to an imaging moiety.
1 . A composition, comprising:
an imaging agent comprising pyridaben or a pyridaben analog attached to an imaging moiety; and
ascorbic acid,
wherein the pH of the composition is between about 1.5 and 3.5 and wherein ascorbic acid is present at a concentration between about 20 mg/mL and about 200 mg/mL ascorbic acid.
2 - 8 . (canceled)
9 . The composition of claim 1 , wherein the composition further comprises water.
10 . The composition of claim 1 , wherein the composition further comprises acetonitrile.
11 . A diagnostic composition, comprising:
an imaging agent comprising pyridaben or a pyridaben analog attached to an imaging moiety; and
ascorbic acid,
wherein the pH of the composition is between about 4.5 and 7.5, and wherein ascorbic acid is present in a concentration between about 20 mg/mL and about 200 mg/mL.
12 - 18 . (canceled)
19 . The composition of claim 11 , further comprising water.
20 . The composition of claim 11 , further comprising an alcohol.
21 . The composition of claim 20 , wherein the alcohol is ethanol.
22 . The composition of claim 21 , wherein ethanol is present in less than about 5% by volume.
23 . The composition of claim 21 , wherein ethanol is present in about 5% by volume, or about 4% by volume, or about 3% by volume, or about 2% by volume, or about 1% by volume.
24 . The composition of claim 11 , wherein the radioactive concentration of the composition is about 1 mCi/mL, about 2 mCi/mL, about 3 mCi/mL, about 4 mCi/mL, about 5 mCi/mL, about 6 mCi/mL, about 7 mCi/mL, about 8 mCi/mL, about 9 mCi/mL, or about 10 mCi/mL.
25 . The composition of claim 1 , wherein the radioactive concentration of the composition is between about 1 mCi/mL and about 200 mCi/mL.
26 . The composition of claim 11 , wherein the radioactive concentration of the composition is less than or equal to about 65 mCi/mL.
27 . The composition of claim 1 , wherein the composition has a radiochemical purity of at least about 95%.
28 . (canceled)
29 . The composition of claim 27 , wherein the composition has a radiochemical purity of at least 95% for at least 12 hours.
30 . (canceled)
31 . The composition of claim 1 , wherein the imaging agent has a structure as in formula (I),
wherein:
J is selected from N(R 9 ), S, O, C(═O), C(═O)O, NHCH 2 CH 2 O, a bond, or C(═O)N(R 7 );
when present, K is selected from hydrogen, alkoxyalkyl, alkyloxy, aryl, C 1 -C 6 alkyl, heteroaryl, and an imaging moiety;
when present, L is selected from hydrogen, alkoxyalkyl, alkyloxy, aryl, C 1 -C 6 alkyl, heteroaryl, and an imaging moiety;
M is selected from hydrogen, alkoxyalkyl, alkyloxy, aryl, C 1 -C 6 alkyl, heteroaryl, and an imaging moiety; or
L and M, together with the atom to which they are attached, form a three-, four-, five-, or six-membered carbocyclic ring;
Q is halo or haloalkyl;
n is 0, 1, 2, or 3;
R 1 , R 2 , R 7 , and R 9 are independently selected from hydrogen, C 1 -C 6 alkyl, and an imaging moiety;
R 3 , R 4 , R 5 , and R 6 are independently selected from hydrogen, halogen, hydroxyl, alkyloxy, C 1 -C 6 alkyl, and an imaging moiety;
R 8 is C 1 -C 6 alkyl; and
Y is selected from a bond, carbon, and oxygen; provided that when Y is a bond, K and L are absent and M is selected from aryl and heteroaryl; and provided that when Y is oxygen, K and L are absent and M is selected from hydrogen, alkoxyalkyl, aryl, C 1 -C 6 alkyl, and heteroaryl;
wherein each occurrence of alkoxyalkyl, alkyloxy, aryl, C 1 -C 6 alkyl, and heteroaryl is optionally substituted with an imaging moiety,
provided that at least one imaging moiety is present in formula (I).
32 . The composition of claim 31 , wherein:
J is O;
M is selected from alkoxyalkyl, alkyloxy, aryl, C 1 -C 6 alkyl, and heteroaryl, each optionally substituted with an imaging moiety;
Q is halo or haloalkyl;
n is 1; and
R 8 is C 1 -C 6 alkyl.
33 - 37 . (canceled)
38 . The composition of claim 1 , wherein the imaging moiety is a radioisotope for nuclear medicine imaging, a paramagnetic species for use in MRI imaging, an echogenic entity for use in ultrasound imaging, a fluorescent entity for use in fluorescence imaging, or a light-active entity for use in optical imaging.
39 - 41 . (canceled)
42 . The composition of claim 38 wherein the imaging moiety is 18 F.
43 . The composition of claim 1 , wherein the imaging agent is selected from the group consisting of
44 . A method comprising administering the composition of claim 1 to a subject; and obtaining an image of the subject.
45 - 49 . (canceled)
50 . The composition of claim 11 , wherein the composition has a radiochemical purity of at least about 95%.
51 . The composition of claim 50 , wherein the composition has a radiochemical purity of at least 95% for at least 12 hours.
52 . The composition of claim 11 , wherein the imaging agent has a structure as in formula (I),
wherein:
J is selected from N(R 9 ), S, O, C(═O), C(═O)O, NHCH 2 CH 2 O, a bond, or C(═O)N(R 7 );
when present, K is selected from hydrogen, alkoxyalkyl, alkyloxy, aryl, C 1 -C 6 alkyl, heteroaryl, and an imaging moiety;
when present, L is selected from hydrogen, alkoxyalkyl, alkyloxy, aryl, C 1 -C 6 alkyl, heteroaryl, and an imaging moiety;
M is selected from hydrogen, alkoxyalkyl, alkyloxy, aryl, C 1 -C 6 alkyl, heteroaryl, and an imaging moiety; or
L and M, together with the atom to which they are attached, form a three-, four-, five-, or six-membered carbocyclic ring;
Q is halo or haloalkyl;
n is 0, 1, 2, or 3;
R 1 , R 2 , R 7 , and R 9 are independently selected from hydrogen, C 1 -C 6 alkyl, and an imaging moiety;
R 3 , R 4 , R 5 , and R 6 are independently selected from hydrogen, halogen, hydroxyl, alkyloxy, C 1 -C 6 alkyl, and an imaging moiety;
R 8 is C 1 -C 6 alkyl; and
Y is selected from a bond, carbon, and oxygen; provided that when Y is a bond, K and L are absent and M is selected from aryl and heteroaryl; and provided that when Y is oxygen, K and L are absent and M is selected from hydrogen, alkoxyalkyl, aryl, C 1 -C 6 alkyl, and heteroaryl;
wherein each occurrence of alkoxyalkyl, alkyloxy, aryl, C 1 -C 6 alkyl, and heteroaryl is optionally substituted with an imaging moiety,
provided that at least one imaging moiety is present in formula (I).
53 . The composition of claim 52 , wherein:
J is O;
M is selected from alkoxyalkyl, alkyloxy, aryl, C 1 -C 6 alkyl, and heteroaryl, each optionally substituted with an imaging moiety;
Q is halo or haloalkyl;
n is 1; and
R 8 is C 1 -C 6 alkyl.
54 . The composition of claim 11 , wherein the imaging moiety is a radioisotope for nuclear medicine imaging, a paramagnetic species for use in MRI imaging, an echogenic entity for use in ultrasound imaging, a fluorescent entity for use in fluorescence imaging, or a light-active entity for use in optical imaging.
55 . The composition of claim 54 wherein the imaging moiety is 18 F.
56 . The composition of claim 11 , wherein the imaging agent is selected from the group consisting of
57 . A method comprising administering the composition of claim 11 to a subject; and obtaining an image of the subject.